Stem cells for diabetic foot ulcers

NewsBot · Oct 5, 2024

The Use of Autologous Cell Therapy in Diabetic Patients with Chronic Limb-Threatening Ischemia
Dominika Sojakova et al
Int J Mol Sci. 2024 Sep 23;25(18):10184

Autologous cell therapy (ACT) is primarily used in diabetic patients with chronic limb-threatening ischemia (CLTI) who are not candidates for standard revascularization. According to current research, this therapy has been shown in some studies to be effective in improving ischemia parameters, decreasing the major amputation rate, and in foot ulcer healing. This review critically evaluates the efficacy of ACT in patients with no-option CLTI, discusses the use of mononuclear and mesenchymal stem cells, and compares the route of delivery of ACT. In addition to ACT, we also describe the use of new revascularization strategies, e.g., nanodiscs, microbeads, and epigenetics, that could enhance the therapeutic effect. The main aim is to summarize new findings on subcellular and molecular levels with the clinical aspects of ACT.
Click to expand...

NewsBot · Oct 24, 2024

Analysis of mRNA expression profile in the treatment of diabetic foot ulcer healing by tibial cortex transverse distraction
Zhi-Qiang Fan et al
Sci Rep. 2024 Oct 22;14(1):24865

To investigate mRNA Expression profile and associated signaling pathways in the treatment of diabetic foot ulcer healing by tibial cortex transverse distraction. Tissue samples were collected from the wound edge before and after the surgery. After reference genome transcriptome sequencing and subsequent bioinformatics analysis, the differentially expressed genes and related pathways were explored, and functional analysis of important genes and pathways was conducted. qRT-PCR was used to verify the significantly expressed genes-HLA-DRB1, HLA-DRB5, CXCL5 and IGFL1. There were 2441 significantly up-regulated and 3904 significantly down-regulated genes in the postoperative group. The qRT-PCR results showed the expression of HLA-DRB1, HLA-DRB5 and CXCL5 was consistent with the transcriptional sequencing results. CXCL5 and CXCL6 differentially up-regulated genes are involved in the process of neovascularization, and HLA-DRB1 is involved in the improvement of the degree of diabetic peripheral nerve degeneration. Pathway analysis showed that differential genes were most significantly enriched in Adherens junction, Inflammatory mediator regulation of TRP channels and Wnt signaling pathway. Inflammatory mediator regulation of TRP channels is involved in the improvement of peripheral neurodegeneration, VEGF signaling pathway is involved in the process of neovascularization, and Wnt signaling pathway is involved in the process of bone healing. Significantly up-regulated CXCL5 and CXCL6 and enriched VEGF signaling pathway analyzed are involved in postoperative lower limb neovascularization. The HLA-DRB1 and the enriched Inflammatory mediator regulation of TRP channels may be related to the improvement of postoperative peripheral neurodegeneration. The differentially expressed genes and related pathways can provide objective basis for further mechanism study.
Click to expand...

NewsBot · Oct 25, 2024

The emerging modulators of non-coding RNAs in diabetic wound healing
Sis Aghayants et al
Front Endocrinol (Lausanne). 2024 Oct 8

Diabetic wound healing is a complex physiological process often hindered by the underlying metabolic dysfunctions associated with diabetes. Despite existing treatments, there remains a critical need to explore innovative therapeutic strategies to improve patient outcomes. This article comprehensively examines the roles of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in regulating key phases of the wound healing process: inflammation, angiogenesis, re-epithelialization, and tissue remodeling. Through a deep review of current literature, we discuss recent discoveries of ncRNAs that have been shown to either promote or impair the wound healing process in diabetic wound healing, which were not covered in earlier reviews. This review highlights the specific mechanisms by which these ncRNAs impact cellular behaviors and pathways critical to each healing stage. Our findings indicate that understanding these recently identified ncRNAs provides new insights into their potential roles in diabetic wound healing, thereby contributing valuable knowledge for future research directions in this field.
Click to expand...

NewsBot · Nov 4, 2024

Mesenchymal stem cell therapy in diabetic foot ulcer: An updated comprehensive review
Helal F Hetta et al
Health Sci Rep. 2024 Apr 21;7(4):e2036

Background
Diabetes has evolved into a worldwide public health issue. One of the most serious complications of diabetes is diabetic foot ulcer (DFU), which frequently creates a significant financial strain on patients and lowers their quality of life. Up until now, there has been no curative therapy for DFU, only symptomatic relief or an interruption in the disease's progression. Recent studies have focused attention on mesenchymal stem cells (MSCs), which provide innovative and potential treatment candidates for several illnesses as they can differentiate into various cell types. They are mostly extracted from the placenta, adipose tissue, umbilical cord (UC), and bone marrow (BM). Regardless of their origin, they show comparable features and small deviations. Our goal is to investigate MSCs' therapeutic effects, application obstacles, and patient benefit strategies for DFU therapy.

Methodology
A comprehensive search was conducted using specific keywords relating to DFU, MSCs, and connected topics in the databases of Medline, Scopus, Web of Science, and PubMed. The main focus of the selection criteria was on English‐language literature that explored the relationship between DFU, MSCs, and related factors.

Results and Discussion
Numerous studies are being conducted and have demonstrated that MSCs can induce re‐epithelialization and angiogenesis, decrease inflammation, contribute to immunological modulation, and subsequently promote DFU healing, making them a promising approach to treating DFU. This review article provides a general snapshot of DFU (including clinical presentation, risk factors and etiopathogenesis, and conventional treatment) and discusses the clinical progress of MSCs in the management of DFU, taking into consideration the side effects and challenges during the application of MSCs and how to overcome these challenges to achieve maximum benefits.

Conclusion
The incorporation of MSCs in the management of DFU highlights their potential as a feasible therapeutic strategy. Establishing a comprehensive understanding of the complex relationship between DFU pathophysiology, MSC therapies, and related obstacles is essential for optimizing therapy outcomes and maximizing patient benefits.
Click to expand...

NewsBot · Nov 5, 2024

Exosome-based cell therapy for diabetic foot ulcers: Present and prospect
Zhou Yang et al
Heliyon. 2024 Oct 11;10(20):e39251

Diabetic foot ulcers (DFUs) represent a serious complication of diabetes with high incidence, requiring intensive treatment, prolonged hospitalization, and high costs. It poses a severe threat to the patient's life, resulting in substantial burdens on patient and healthcare system. However, the therapy of DFUs remains challenging. Therefore, exploring cell-free therapies for DFUs is both critical and urgent. Exosomes, as crucial mediators of intercellular communication, have been demonstrated potentially effective in anti-inflammation, angiogenesis, cell proliferation and migration, and collagen deposition. These functions have been proven beneficial in all stages of diabetic wound healing. This review aims to summarize the role and mechanisms of exosomes from diverse cellular sources in diabetic wound healing research. In addition, we elaborate on the challenges for clinical application, discuss the advantages of membrane vesicles as exosome mimics in wound healing, and present the therapeutic potential of exosomes and their mimetic vesicles for future clinical applications.
Click to expand...

NewsBot · Nov 11, 2024

Multi-target gene therapy AUP1602-C to improve healing and quality of life for diabetic foot ulcer patients: a phase I, open-label, dose-finding study
Christoph Schindler et al
Source

Background: Diabetic foot ulcer (DFU) is a common and highly morbid complication of diabetes with high unmet medical needs. AUP1602-C, a topical four-in-one gene therapy medicinal product (GTMP), consisting of a Lactococcus cremoris strain that produces fibroblast growth factor-2, interleukin-4, and colony-stimulating factor-1, is a promising novel treatment for DFU. Objectives: The aim of this first-in-human study was to investigate whether AUP1602-C is safe and effective in improving wound healing and quality of life (QoL) in patients with non-healing DFU (nhDFU), and to determine the recommended phase II dose. Design: Phase I, single-arm, open-label, uncontrolled, dose escalation study. Methods: The study consisted of four cohorts of patients receiving AUP1602-C as a single dose of 2.5 × 105 colony-forming units (CFU)/cm2 ulcer size or as repeated doses between 2.5 × 106 and 2.5 × 108 CFU/cm2 administered 3 times per week for 6 weeks. Within each cohort, a 3 + 3 scheme for monitoring safety, tolerability, and efficacy was applied. Results: In total, 16 patients aged 53–80 years were included, 3 each in the safety and low dose, 4 in the medium dose, and 6 in the high-dose cohort. AUP1602-C demonstrated a favorable safety profile with almost 100% dosing compliance. The most frequently reported side effect related to treatment was skin maceration. No serious adverse reactions, systemic toxicity, deaths, or side effects suggestive of immunogenicity, hypersensitivity, allergic reaction, or dose-limiting toxicities related to treatment were reported. No biodistribution events were observed and shedding-related events were rare and did neither show accumulation nor dose dependency. The recommended phase II dose of 2.5 × 108 CFU/cm2 demonstrated complete healing in 83% of patients without recurrence of ulcers during followup. Conclusion: AUP1602-C was safe and well tolerated and demonstrated dose-dependent efficacy in patients with nhDFU. Data supports further clinical development of AUP1602-C.
Click to expand...

NewsBot · Nov 11, 2024

Biofriendly resveratrol loaded glycerosomal nanovesicles improve wound healing in chronic diabetic foot ulcers: In-vitro & in-vivo efficacy evaluation
Marwa Belal et al
Journal of Drug Delivery Science and Technology
Volume 97, August 2024, 105805

Chronic diabetic foot ulcers (CDFUs) are complex pathological processes involving persistent inflammation, significantly impacting a patient's quality of life. Resveratrol (RES), recognized for its potent antioxidant and anti-inflammatory properties, faces challenges regarding its permeability. This study aimed to develop Resveratrol glycerosomal nanovesicles (RES-GLY-NVs) for topical application to enhance skin permeation. The optimized formulation was integrated into a 2 % HPMC gel and subjected to comprehensive physicochemical characterization, skin deposition, in vitro release, microbiological, antioxidant, and in vivo assessments. Results revealed RES-GLY-NVs with particle size ranging from 82.19 ± 6.51 nm to 145.70 ± 1.39 nm with PDI less than 0.5, encapsulation efficacy ranging from 89.14 ± 1.39 % to 96.09 ± 2.13 % and a zeta potential ranging from −27.93 ± 6.47 mV to −49.33 ± 1.89 mV. The release profile of RES was obviously ranging from % 54.40 ± 1.71 to 77.47 ± 0.54 % after 8 h. In vitro cell assessment revealed that RES-GLY-NVs have no cytotoxicity on normal cells. The optimized RES-GLY-NVs-HPMC gel displayed pseudoplastic rheological behavior and significantly enhanced RES flux and permeability through excised rat skin compared to plain gel. The In vivo study and histological evaluation of diabetic rats ensured that RES-GLY-NVs-HPMC gel acts as a more effective healing adjunct compared to free RES and conventional therapy. These findings encourage the utilization of RES-GLY-NVs-HPMC gel as a wound-healing drug delivery system in chronic diabetes-related wounds and ulcers.
Click to expand...

NewsBot · Nov 16, 2024

Autologous cell therapy for ischemic diabetic foot: a meta-analysis of randomized controlled trials for the development of the Italian guidelines for the treatment of diabetic foot syndrome
Alessia Scatena et al
Acta Diabetol. 2024 Nov 15

Aim: To assess the efficacy and safety of autologous cell therapy (ACT) in patients with ischemic diabetic foot ulcers (DFU). The present meta-analysis was designed to support the development of the Italian Guidelines for the Treatment of Diabetic Foot Syndrome (DFS).

Methods: A Medline and Embase search were performed up to Feb 1st, 2024 collecting all RCTs including diabetic patients or reporting subgroup analyses on diabetic patients with ischemic foot ulcers comparing ACT with placebo/no therapy/standard of care (SoC), with a duration of at least 26 weeks. Prespecified endpoints were: major amputation (principal) and minor amputation, ulcer healing, time-to-healing, transcutaneous oxygen pressure (TcPO2), ankle-brachial index (ABI), pain, and all-cause mortality (secondary). Any ACT was allowed, irrespective of cell product type and route of administration (intra-arterial and intramuscular).

Results: Seven studies fulfilled all inclusion criteria, all using intramuscular transplantation as route of administration, but only 2 had a follow-up greater than 26 weeks. Participants treated with ACT had a significantly lower risk of major amputations in comparison with SoC/placebo (MH-OR 0.47 [0.24, 0.92], p = 0.03). ACT was also associated with a significantly higher rate of ulcer healing (MH-OR: 10.1 [3.5, 29.6], p < 0.001), greater increase of TcPO2 and ABI values (WMD: 17.57 [13.02, 22.12], p < 0.001), and reduction of pain (WMD: -1.83 [-2.32, -1.34], p = 0.003).

Conclusions: ACT must be considered as a potential therapy for patients with ischemic diabetic foot ulcers. Further studies are needed to better clarify their role in the treatment and management of DFS.
Click to expand...

NewsBot · Nov 25, 2024

Effectiveness of Stem Cell Therapy for Diabetic Foot Ulcers: Cell Therapy Alone is Not Enough for Effective Management of Chronic Wounds
Ekaterina Evstratova, et al
Source

We read with great interest the meta-analysis by Mudgal et al. (2024) regarding the effectiveness and safety assessment of stem cell therapy for diabetic foot ulcers. Indeed, The management of chronic wounds requires innovative approaches to avoid unsuccessful outcomes, and stromal cell therapies have emerged as a potential solution for soft tissue repair. A critical aspect of this therapeutic strategy is the role of mast cells in stimulating delayed inflammation through their interactions with various cells as well as the extracellular matrix. Mast cells are critical in orchestrating the inflammatory response and their activation can influence macrophage behavior and secondary healing efficacy. The use of mesenchymal stromal cells in regenerative medicine for diabetic foot ulcers treatment is often limited by their time-limited anti-inflammatory responses. However, these time-limited effects could not achieve the prolonged effects and impact of cell therapy efficacy and the potential enhancement of cell function by biologically active factors such as growth factors or gene therapeutics for prolonged release. The integration of cell and prolonged release gene therapeutics is a promising approach that goes beyond regenerative medicine by preventing secondary inflammatory complications. While mesenchymal stromal cells have shown promising results in experimental and clinical studies, there are limitations to their efficacy in regenerative medicine for diabetic foot ulcers. These limitations include the heterogeneity of cell populations used in the studies, the difficulty in determining the contribution of cells when used in combination with materials, the lack of data on optimal cell numbers for tissue repair, the effect of culture conditions on cell therapy efficacy, and the potential enhancement of cell efficacy by the use of additional biologics such as growth factors or gene therapeutics. The combination of cell and gene therapy is seen as a promising approach that goes beyond regenerative medicine into the field of molecular surgery of chronic wounds.
Click to expand...

NewsBot · Dec 7, 2024

Role of microRNAs in diabetic foot ulcers: Mechanisms and possible interventions
Lin Wang et al
Diabetes Research and Clinical Practice Volume 217, November 2024, 111858

Highlights
•miRNAs are closely associated with the development and prognosis of DFUs.
•miRNAs can serve as diagnostic biomarkers and therapeutic targets for DFUs.
•miRNAs are involved in regulating the immune response, inflammation, angiogenesis, and epithelialization in DFUs.
•The main limitations of miRNA therapy for DFUs include delivery challenges, safety risks, and limited clinical research.
Click to expand...

Diabetic foot ulcer (DFU) is a common and serious complication among diabetic patients, and its incidence and difficulty in treatment have placed large burdens on patient health and quality of life. Diabetic foot tissue typically exhibits chronic wounds, ulcers, or necrosis that are difficult to heal, are prone to infection, and, in severe cases, may even lead to amputation. Recent studies have shown that microRNAs (miRNAs) play key roles in the development and healing of DFUs. miRNAs are a class of short noncoding RNA molecules that regulate gene expression to affect cellular functions and physiological processes. miRNAs may be involved in the development of DFUs by regulating cell growth, proliferation, differentiation and apoptosis. miRNAs can also participate in the healing and recovery of DFUs by regulating key steps, such as inflammation, angiogenesis, cell migration and proliferation, tissue repair and matrix remodeling. Therefore, altering the pathological processes of diabetic foot by modulating the expression of miRNAs could improve the recovery and treatment outcomes of patients. This review provides new insights and perspectives for the treatment of DFUs by summarizing the roles of miRNAs in the development and healing of DFUs and the mechanisms.
Click to expand...

NewsBot · Dec 14, 2024

Placenta-Derived Biomaterials vs. Standard Care in Chronic Diabetic Foot Ulcer Healing: A Systematic Review and Meta-Analysis
Maria Ruiz-Muñoz et al
Diabetes & Metabolic Syndrome: Clinical Research & Reviews 10 December 2024, 103170

Highlights
•Diabetes foot patients often require extended hospital stays due to foot issues, a leading cause of hospitalization.
•Fifteen percent of diabetics develop foot disease, with 25% facing lower limb amputation.
•Placenta biomaterials include tissues from amniotic fluid, sac, umbilical cord, placental disc, and mixtures.
•Treatment group has 6.24 times higher ulcer closure rate compared to random closure in conventional treatment.
Click to expand...

Introduction
This study explored the effectiveness of current placenta-derived biomaterials therapies in ulcer healing in DFU compared to standard of care (SOC).
Methods
The systematic review and meta-analysis were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard. The electronic databases of PubMed, EMBASE, and Web of Science (WoS) internet were searched for the outcome rate of complete ulcer healing. The risk of bias assessment was conducted using the tool recommended by the Cochrane Collaboration. Statistical analysis included the individual and combined result of the studies, heterogeneity test, the effect size, sensitivity analysis, and publication bias tests.
Results
Twelve randomized controlled trials (RCTs) with a total of 833 patients were included in this study. This meta-analysis showed a higher rate of complete ulcer healing in groups receiving placenta-derived biomaterials therapies (OR = 6.247 [4.425, 8.819], p < 0.01, I2 = 41%) compared to control groups.
Conclusion
Placenta-derived biomaterials therapies have been shown to be more effective for achieving complete ulcer healing compared to current conventional treatments in DFU.
Implications for Clinical Practice
The utilization of placenta-derived biomaterials in therapies for wound healing, particularly in chronic DFU, presents promising implications for clinical practice. These biomaterials offer a rich source of growth factors, cytokines, and extracellular matrix components, which can stimulate tissue regeneration and angiogenesis. Incorporating such therapies into clinical practice holds the potential to accelerate wound closure, reduce infection rates, and improve overall healing outcomes in people with diabetic chronic foot ulcers. Furthermore, the availability of these biomaterials can offer clinicians a readily-accessible and cost-effective alternative to traditional wound care approaches, ultimately enhancing patient care and quality of life.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Click to expand...

NewsBot · May 7, 2025

Comparative Efficacy of Regenerative Therapies for Diabetic Foot Ulcers: A Network Meta-analysis
Hsi-An Yang, Ren-Jun Hsu, Wun-Long Jheng, Feng-Ju Weng, Jian-Jr Lee
Ann Plast Surg. 2025 Mar 1;94(3S Suppl 1):S24-S32.

Background: Diabetic foot ulcer (DFU) is one of the most dreaded complications of diabetes mellitus and is associated with a high risk of lower limb amputation and mortality. Because the efficacy of conventional treatments for DFUs is often limited, regenerative medicine therapy, such as growth factors and stem cells, may provide a solution to chronic wound healing. In this study, we compared several kinds of regenerative therapy for treating DFUs in terms of efficacy.

Methods: We systemically searched relevant studies on PubMed, Cochrane Library, and EMBASE. Randomized clinical trials on conventional treatment combined with platelet-rich plasma (PRP), epidermal growth factor (EGF), or stem cell therapy, compared with conventional treatment alone in patients with DFUs, were included in this study.

Results: A total of 1454 patients from 23 randomized controlled trials (RCTs) were included in the network meta-analysis. In terms of the number of completely healed ulcers, no significant difference was noted between PRP, stem cell therapy, and EGF group. We also performed surface under the cumulative ranking curve analyses to predict the rank of each intervention by the number of completely healed ulcers. The predicted ranking was as follows: stem cell, PRP, EGF, and the control group (conventional treatment alone). Furthermore, when we compared the mean of the wound healing time of DFUs among these four interventions, we found that the PRP group achieved significantly earlier ulcer healing than the stem cell, EGF, and control groups. No significant difference was observed in the time needed for wound healing between the stem cell and EGF groups. Funnel plot analysis demonstrated no publication bias.

Conclusions: PRP combined with conventional treatment significantly accelerates wound healing for DFUs. The mean wound healing time was similar between the stem cell and EGF groups. However, additional reviews of rigorous, large, well-designed RCTs are warranted for further validation of our findings.
Click to expand...

NewsBot · Jun 18, 2025

Adipose-derived Stem Cells for Treatment of Diabetic Foot Ulcers: A Review
Prithiviraj Nagarajan et al
Curr Stem Cell Res Ther. 2025;20(5):509-523.

This study investigates the therapeutic potential of adipose-derived stem cells (ASCs) in diabetic foot ulcers (DFUs). The goal is to further research regenerative medicine by improving knowledge of ASC-based therapies in diabetic wound management. A comprehensive literature review included studies from reputable databases, including PubMed and the Cochrane Library. We paid particular attention to the clinical, in vivo, and in vitro investigations of the utility and effectiveness of ASCs in treating DFU. We also highlighted novel isolation techniques and application methods for ASCs in chronic wound management. ASCs have shown great potential in regenerative interventions for diabetes, especially in DFU management. These cells facilitate wound repair by differentiating into different cell types, promoting angiogenesis, secreting growth factors, reducing inflammation, and increasing wound perfusion. However, the current body of research on ASC applications for DFU still requires further investigation. This shows the importance of thoroughly studying their biological mechanisms and therapeutic uses. This review establishes that ASC-based treatments effectively enhance outcomes for patients suffering from DFU. We recommend further investigation of the functionality of ASCs and therapeutic approaches to maximize their therapeutic potential in managing diabetic wounds, thereby advancing the development of regenerative medicine.
Click to expand...

NewsBot · Jun 18, 2025

Adipose-Derived Mesenchymal Stem Cells Accelerate Diabetic Foot Ulcer Healing by Promoting Macrophage M2 Polarization Through Downregulation of EREG and CSTA
Jing Cao et al
J Inflamm Res. 2025 Jun 12:18:7749-7768.

Purpose: Macrophage polarization plays a critical role in the chronic wound healing of diabetic foot ulcers (DFU). Recent studies have shown that adipose-derived mesenchymal stem cells (ADSCs) can reduce inflammation in DFU and promote wound healing. Despite advances in stem cell therapy, the molecular mechanisms by which ADSCs regulate macrophage polarization in DFU healing remain unclear, and robust prognostic models for DFU are lacking. This study aims to identify macrophage polarization-associated molecules in DFU and explore whether ADSCs promote DFU healing by regulating these molecules.

Patients and methods: Macrophage polarization-associated differentially expressed genes (MA-DEGs) were screened from GSE134431 and GSE80178 datasets. Protein-protein interaction (PPI) networks were constructed using STRING and Cytoscape. Machine learning and Firth regression were employed to develop a prognostic model, which was evaluated using receiver operating characteristic (ROC) curves. The expression of predicted genes (EREG and CSTA) and the regulatory effects of ADSCs on these genes were validated in both DFU mouse model and THP-1 cells.

Results: A total of 30 macrophage polarization-associated differentially expressed genes (MA-DEGs) were identified, including 18 hub genes. These MA-DEGs were primarily enriched in pathways related to leukocyte chemotaxis and interleukin-4 and 13. A two-gene prognostic model was constructed using machine learning and Firth regression, achieving an AUC greater than 0.944 in both the training and external validation datasets. In vivo and in vitro experiments demonstrated that ADSCs regulate EREG and CSTA expression to promote macrophage M2 polarization and facilitate DFU wound healing.

Conclusion: This study elucidates the molecular mechanisms by which ADSCs facilitate DFU healing via macrophage M2 polarization. The identified two-gene MA-DEGs model not only serves as a potential prognostic biomarker but also provides promising targets for DFU therapy.
Click to expand...

NewsBot · Jun 18, 2025

Efficacy of Mesenchymal Stem Cells in the Treatment of Diabetic Foot Ulcers: A Meta-Analysis of Randomized Controlled Trials
Xiang-Hui Mei et al
Int J Low Extrem Wounds. 2025 Jun 18:15347346251348797.

BackgroundDiabetic foot ulcers (DFUs), a severe chronic complication of diabetes, are characterized by refractory wounds and high risks of amputation/mortality, posing substantial public health challenges. Mesenchymal stem cells (MSCs) demonstrate therapeutic potential through synergistic mechanisms including paracrine signaling, immunomodulation, neovascularization, and tissue regeneration. This study conducts a systematic review and meta-analysis of randomized controlled trials (RCTs) to comprehensively evaluate the clinical efficacy of MSC-based therapy for DFUs, aiming to optimize treatment strategies with evidence-based insights.MethodWe systematically searched PubMed, Embase, Cochrane Library, and Web of Science for RCTs investigating MSC therapy in DFUs. Following PRISMA guidelines, studies were selected with pre-defined criteria. Meta-analyses employed random-/fixed-effects models based on I2 statistics. Primary endpoints encompassed complete healing rate (100% epithelialization), amputation incidence, serious adverse events (SAEs) risk, and recurrence rate. Furthermore, sensitivity analyses were conducted to evaluate the robustness of the findings. A comprehensive assessment of potential publication bias in the current meta-analysis was performed using Egger's linear regression test, Begg's rank correlation test, and funnel plot visualization.ResultsSix RCTs were included. MSC therapy significantly improved overall complete healing rates (RR = 1.63, 95% CI: 1.23-2.16; P = .0007), particularly in small ulcers (<5 cm2; RR = 1.71, 1.11-2.63, P = .02), but showed no efficacy for large ulcers (≥5 cm2; RR = 1.18, 0.75-1.86, P = .46). No significant differences emerged in amputation risk (P = .16), serious adverse events (P = .38), and recurrence (P = .33). Low heterogeneity and no publication bias were observed.ConclusionThis meta-analysis demonstrates MSCs therapy significantly enhances wound closure in diabetic foot ulcers, particularly achieving in small ulcers. However, no stable therapeutic benefits were observed for large ulcers, amputation prevention, recurrence reduction, and SAEs. Future multicenter phase III trials with standardized protocols are warranted to establish ulcer stage/size-specific treatments.
Click to expand...

NewsBot · Jun 22, 2025

Efficacy of Mesenchymal Stem Cells in the Treatment of Diabetic Foot Ulcers: A Meta-Analysis of Randomized Controlled Trials
Xiang-Hui Mei et al
Source

Background
Diabetic foot ulcers (DFUs), a severe chronic complication of diabetes, are characterized by refractory wounds and high risks of amputation/mortality, posing substantial public health challenges. Mesenchymal stem cells (MSCs) demonstrate therapeutic potential through synergistic mechanisms including paracrine signaling, immunomodulation, neovascularization, and tissue regeneration. This study conducts a systematic review and meta-analysis of randomized controlled trials (RCTs) to comprehensively evaluate the clinical efficacy of MSC-based therapy for DFUs, aiming to optimize treatment strategies with evidence-based insights.
Method
We systematically searched PubMed, Embase, Cochrane Library, and Web of Science for RCTs investigating MSC therapy in DFUs. Following PRISMA guidelines, studies were selected with pre-defined criteria. Meta-analyses employed random-/fixed-effects models based on I2 statistics. Primary endpoints encompassed complete healing rate (100% epithelialization), amputation incidence, serious adverse events (SAEs) risk, and recurrence rate. Furthermore, sensitivity analyses were conducted to evaluate the robustness of the findings. A comprehensive assessment of potential publication bias in the current meta-analysis was performed using Egger's linear regression test, Begg's rank correlation test, and funnel plot visualization.
Results
Six RCTs were included. MSC therapy significantly improved overall complete healing rates (RR = 1.63, 95% CI: 1.23-2.16; P = .0007), particularly in small ulcers (<5 cm2; RR = 1.71, 1.11-2.63, P = .02), but showed no efficacy for large ulcers (≥5 cm2; RR = 1.18, 0.75-1.86, P = .46). No significant differences emerged in amputation risk (P = .16), serious adverse events (P = .38), and recurrence (P = .33). Low heterogeneity and no publication bias were observed.
Conclusion
This meta-analysis demonstrates MSCs therapy significantly enhances wound closure in diabetic foot ulcers, particularly achieving in small ulcers. However, no stable therapeutic benefits were observed for large ulcers, amputation prevention, recurrence reduction, and SAEs. Future multicenter phase III trials with standardized protocols are warranted to establish ulcer stage/size-specific treatments.
Click to expand...

NewsBot · Jul 11, 2025

Comparison of the efficacy and safety of different growth factors in the treatment of diabetic foot ulcers: an updated network meta-analysis
Jianzhou Tian et al
Front Endocrinol (Lausanne). 2025 Jun 25:16:1614597.

Objective: This study aimed to evaluate the efficacy and safety of different growth factors (GFs) in the treatment of diabetic foot ulcers (DFUs) through a network meta-analysis.

Methods: A systematic search was conducted in PubMed, Embase, The Cochrane Library, and Web of Science to identify randomized controlled trials (RCTs) comparing GFs with standard of care (SOC) or comparing different GFs for the treatment of DFU. Two independent reviewers screened the studies, extracted data, and assessed the quality of the included literature according to predefined inclusion and exclusion criteria. A network meta-analysis was performed using R software. Relative risk (RR) was used as the effect measure for dichotomous outcomes, and mean difference (MD) was used for continuous outcomes.

Results: A total of 51 RCTs, involving 3,401 patients with DFUs and six different types of GFs, were included. The network meta-analysis revealed that, compared with SOC, epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and platelet-rich plasma (PRP) significantly improved the healing rate. EGF and PRP also significantly reduced healing time, while PDGF significantly reduced ulcer area. Moreover, PRP was associated with a significant reduction in the incidence of adverse events (AEs) and amputation rates. In terms of ranking: For healing rate, the top three GFs were EGF, vascular endothelial growth factor (VEGF), and granulocyte colony-stimulating factor (G-CSF). For healing time, EGF, PRP, and fibroblast growth factor (FGF) ranked the highest. For ulcer area reduction, PDGF, EGF, and PRP were the top-ranking interventions. Regarding AEs, PRP, PDGF, and FGF showed the most favorable safety profiles. For amputation rate, PRP, G-CSF, and PDGF were ranked the highest.

Conclusion: Almost all GFs outperformed SOC in terms of healing rate, healing time, and ulcer area reduction. Compared to SOC, EGF, PDGF, and PRP significantly improved healing rates; EGF and PRP significantly reduced healing time; and PDGF significantly decreased ulcer area. Among them, EGF may be the most effective GF. Except for VEGF, which significantly increased AEs, other GFs did not show a significant increase in AEs compared to SOC. PRP had the lowest amputation rate and incidence of AEs.
Click to expand...

NewsBot · Jul 13, 2025

Advancements in diabetic foot ulcer therapy: The role of exosomes and decellularised extracellular matrix scaffolds
Yanbei Zhu et al
Diabetes Res Clin Pract. 2025 Jul 10:112364.

Diabetic foot ulcer (DFU) ranks among the most severe complications of diabetes mellitus. DFU mainly arises from neuropathy and peripheral arterial disease, with aggravating factors like infection and edema. These ulcers impose significant physical and financial challenges, making wound healing a crucial clinical issue. Current DFU management focuses on ensuring adequate blood flow, relieving pressure, controlling infection, and debridement. Cell therapy offers notable benefits, yet the effectiveness of traditional stem cell transplants for DFU remains contentious. In this context, exosomes are gaining recognition as a promising option in tissue engineering and regenerative medicine. Their advantages include excellent biocompatibility, precise targeting, and ability to cross biological barriers, proficient drug delivery, low toxicity, and abundant availability. Numerous studies indicate that stem cell-derived exosomes contribute to diabetic wound healing by promoting angiogenesis, collagen deposition, and reducing inflammation, among other mechanisms. This acellular approach presents significant advantages over conventional methods and is crucial in DFU management. Nonetheless, challenges such as the limited retention of exosomes at injury sites render singular treatment strategies insufficient for optimal outcomes. By integrating decellularized extracellular matrix (dECM)-based scaffolds with exosomes, enhanced transfer and retention of exosomes can be achieved, along with a sustained release. This review summarizes the role and mechanisms of exosomes from various stem cells in enhancing DFU wound healing, recent advancements in dECM scaffolds, and discusses the application of exosomes combined with dECM scaffolds in DFU therapy, along with the associated challenges.
Click to expand...

NewsBot · Aug 13, 2025

Advances in the Role of Stem Cell-Derived
Exosomes in Diabetic Foot Wound Healing
Junbo Wang et al
Source

Chronic hyperglycemia over a long period can lead to diabetes-related complications, of which diabetic foot ulcers
continue to have a huge economic and social impact worldwide. Mesenchymal stem cell-derived exosomes (MSC-Exos) have
demonstrated positive efficacy in the preclinical research and clinical trial phases of diabetic foot ulcer (DFU) treatment. In this
review, we provide a brief overview of the properties of MSC-derived exosomes and their biological functions, summarize the
therapeutic efficacy of Exos in the treatment of diabetic foot ulcers and its mechanism of action, and discuss innovative technologies
including hydrogel scaffolds and 3D bioprinting to enhance the effectiveness of MSC - Exos in the treatment of diabetic foot ulcers.
This paper also explores the application of innovative technologies such as hydrogel scaffolds and 3D bioprinting in enhancing the
efficacy of MSC-Exos in the treatment of diabetic foot ulcers and highlights the key challenges faced in translating these advanced
technologies from the laboratory to the clinic
Click to expand...

NewsBot · Oct 4, 2025

A Systematic Review of the Therapeutic Potential Use of Exosomes in Diabetic Foot Ulcers Healing
Roxana Paola Gómez-Ruiz et al
Source

Background: Diabetic foot ulcers (DFUs) a serious complication of diabetes mellitus, often leads to prolonged hospitalization, infection, and limb amputation. Their multifactorial pathogenesis includes chronic inflammation, impaired angiogenesis, oxidative stress, and defective fibroblast activity in recent years, regenerative medicine has gained attention, particularly the use of exosomes derived from adipose-derived mesenchymal stem cells (ADSCs). These exosomes carry bioactive molecules capable of modulating key processes in wound healing, including inflammation resolution, cellular proliferation, migration, and extracellular matrix remodeling. Methodology: A systematic literature review was conducted using PubMed, and Scopus to identify relevant preclinical and clinical studies published up to April, 2025. Search terms included "adipose-derived stem cells," "exosomes," "diabetic foot ulcers," and "wound healing." Studies were selected based on predefined inclusion and exclusion criteria, focusing on mechanistic insights and therapeutic outcomes of ADSC-exos in diabetic wound healing models. Results: From an initial 840 potentially eligible studies, 25 met the predefined inclusion criteria and were incorporated into the final analysis. Conclusion: ADSC-exos improve diabetic fibroblast wound healing by reducing inflammation through macrophage M2 polarization, promoting migration and proliferation of fibroblasts and keratinocytes, and supporting angiogenesis through signaling pathways such as PI3K/AKT, Wnt/β-catenin, and TGF-β/Smad. Together, these actions accelerate epithelial regeneration and granulation tissue formation. Preclinical findings consistently report enhanced healing outcomes, yet translation to human application remains limited. Challenges such as standardization of exosome isolation, dosing, delivery methods, and long-term safety must be addressed prior to clinical implementation. Nonetheless, the current findings support ADSC-Exos as a promising cell-free alternative to stem cell therapy in diabetic wound treatment and may revolutionize treatment strategies for diabetic wounds.
Click to expand...

NewsBot · Oct 16, 2025

Human Mesenchymal Stem Cell Derived Exosomes Endowed with miR-13474 as a Therapeutic Delivery Vehicle for Diabetic Wound Healing by Targeting the CPEB2/TWIST1 Axis
Hui Shi et al
ACS Appl Bio Mater. 2025 Oct 15.

A delayed healing process in diabetic wounds is intractable. In this study, a high-glucose condition was found to be responsible for skin structure destruction, inflammatory infiltration, and vital cell dysfunction. Extracellular vesicles, particularly exosomes secreted by hucMSCs, contribute to improved diabetic wound healing, largely by promoting tissue repair and re-establishing normal function in affected cells. Small RNA-sequencing revealed that hucMSC-derived exosomes (hucMSC-Ex) were highly enriched in NC_000019.10_13474 (miR-13474), which was predicted to be an miRNA with an undiscovered function. miR-13474 showed a reduced expression level in high-glucose-treated skin cells as well as diabetic foot ulcer (DFU) rats. Moreover, there is also a significant expression difference between the wound area and the wound edge in DFU patients, indicating the potential clinical value of miR-13474. Blocking miR-13474 in hucMSC-Ex obviously diminished the therapeutic effects. Furthermore, exosomal miR-13474 was found to target the CPEB2/TWIST1 axis to improve the impaired function of skin cells. On this basis, hucMSC-Ex were used as a vehicle for the delivery of therapeutic miR-13474 to optimize the repairing effect. The study has revealed the role of hucMSC-derived exosomes and the underlying molecular mechanism in diabetic wound healing and proposes a cell-free-based modification strategy for refractory wound management.
Click to expand...

NewsBot · Oct 17, 2025

Human Placenta‐Derived Cells (PDA‐002) in Diabetic Foot Ulcer Patients With and Without Peripheral Artery Disease: A Phase 2 Multi‐Center, Randomised, Double‐Blind, Placebo‐Controlled Trial
Richard Pollak et al
Int Wound J. 2025 Oct 12;22(10):e70769. doi: 10.1111/iwj.70769

The management of diabetic foot ulcers in patients with peripheral artery disease remains challenging. Human placenta‐derived cells (PDA‐002), a mesenchymal stromal cell‐like population obtained from full‐term placental tissue, possess angiogenic and tissue regenerative properties. Participants were stratified based on peripheral artery disease status. A total of 159 individuals were randomly assigned to receive intramuscular PDA‐002 at one of three doses (3 × 106, 10 × 106 and 30 × 106 cells) or a placebo. This Phase 2 multi‐center, randomised, double‐blind, placebo‐controlled trial evaluated adults with chronic diabetic foot ulcers with and without peripheral artery disease. The primary efficacy endpoint was the proportion of participants achieving complete wound closure of the index ulcer within 3 months, with sustained closure maintained for an additional 4 weeks. PDA‐002 was well‐tolerated, with no treatment‐related serious adverse events. Intramuscular PDA‐002 treatment achieved the highest efficacy at the 3 × 106 cell dose within the peripheral artery disease subgroup (38.5% vs. 22.6% for placebo), meeting a stringent 4‐week durability endpoint that surpassed the U.S. Food and Drug Administration's recommended 2‐week sustainability criterion. PDA‐002 shows promise as a breakthrough treatment for diabetic foot ulcers and peripheral artery disease, demonstrating efficacy with two intramuscular doses and no re‐treatment.
Click to expand...

NewsBot · Oct 17, 2025

Use of thermal imaging in the detection of the diabetic foot- review
Reviews in Endocrine and Metabolic Disorders 14 October 2025

Diabetic foot ulcers (DFUs) are among the most serious complications of diabetes mellitus, often resulting in infection, amputation, and increased mortality. Early detection is essential but remains difficult due to the complex interaction of neuropathy, vascular disease, and immune dysfunction. This review examines the effectiveness of thermal imaging, including approaches supported by artificial intelligence (AI), as a non-invasive tool for identifying early signs of DFUs. A total of 49 studies published between 1991 and 2024 were analysed, focusing on adult patients and primary research only. Findings show that thermal imaging can detect abnormal skin temperature patterns and early inflammation, key indicators of DFU development. AI techniques, such as machine learning and neural networks, further enhance diagnostic accuracy by identifying subtle patterns and predicting ulcer risk. Despite promising results, several limitations were noted: lack of standardised imaging protocols, inconsistent equipment quality, and small sample sizes in many studies. To improve clinical reliability, future work should focus on developing standard procedures, integrating AI with high-resolution thermal cameras, and validating these systems in real-world hospital and home-care settings. Overall, thermal imaging, especially when combined with AI, shows strong potential as a practical, non-invasive method for early DFU detection and monitoring.
Click to expand...

Stem cells for diabetic foot ulcers

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

Reprogramming of diabetic foot ulcer cells to create therapeutic stem cell

Stem cells for plantar fasciitis

Crossover Second Toe Syndrome treated by Autologous Peripheral Blood Stem Cells

Stem cells Chondral Defects of the 1st Metatarsophalangeal Joint

Nail stem cells to regrow nails?

Stem Cells

Sweat glands as a source of stem cells for wound healing

Share This Page

Stem cells for diabetic foot ulcers

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

Reprogramming of diabetic foot ulcer cells to create therapeutic stem cell

Stem cells for plantar fasciitis

Crossover Second Toe Syndrome treated by Autologous Peripheral Blood Stem Cells

Stem cells Chondral Defects of the 1st Metatarsophalangeal Joint

Nail stem cells to regrow nails?

Stem Cells

Sweat glands as a source of stem cells for wound healing

Share This Page

Useful Searches