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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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NewsBot · Dec 7, 2024 at 11:13 PM

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.
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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.
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Stem cells for diabetic foot ulcers

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Stem cells for diabetic foot ulcers

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Reprogramming of diabetic foot ulcer cells to create therapeutic stem cell

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

Adult stem cells could hold key to curing Type 1 diabetes

Share This Page

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