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Targeting Nonhealing Ulcers of Lower Extremity in Human Through Autologous Bone Marrow-Derived Mesenchymal Stem Cells
Abstract
Bone marrow (BM)-derived mesenchymal stem cells (MSCs) represent a promising population for supporting new concepts in cellular therapy. This study was undertaken to assess the efficacy and feasibility of autologous BM-derived MSCs in the treatment of chronic nonhealing ulcers (diabetic foot ulcers and Buerger disease) of the lower extremities. A total of 24 patients with nonhealing ulcers of the lower limb were enrolled and randomized into implant and control groups. In the implant group, the patients received autologous cultured BM-derived MSCs along with standard wound dressing; the control group received only the standard wound dressing regimen, followed up for at least a 12-week period. Wound size, pain-free walking distance, and biochemical parameters were measured before therapy and at every 2-week interval following intervention. The implant group had significant improvement in pain-free walking distance and reduction in ulcer size as compared to those in the control group. In the implant group for Buerger disease, the ulcer area decreased from 5.04 ± 0.70 cm 2 to 1.48 ± 0.56 cm 2 ( p < 0.001), whereas the pain-free walking distance increased from 38.33 ± 17.68 m to 284.44 ± 212.12 m ( p < 0.001). In the diabetic foot ulcer group, the ulcer size decreased from 7.26 ± 1.41 cm 2 to 2 ± 0.98 cm 2 ( p < 0.001) at 12 weeks. Mononuclear cells were cultured for a minimum of five passages and characterized by cell-surface markers showing CD90 + , CD105 + , and CD34 − . There was no significant alteration in the biochemical parameters observed during the follow-up period, indicating normal liver and renal function following intervention. Biopsy microsection of implanted tissues showed development of dermal cells (mainly fibroblasts), including mature and immature inflammatory cells. The study indicates that autologous implantation of BM-derived MSCs in nonhealing ulcers accelerates the healing process and improves clinical parameters significantly.
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“Along these lines, clinical studies have shown that bone marrow– and adipose tissue–derived MSCs can augment the repair process when applied locally to chronic skin wounds in patients (96, 150).”
From Wound repair and regeneration: Mechanisms, signaling, and translation (2014) · cites this paper as [150]
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The role of mesenchymal stem/stromal cells in angiogenesis
Bronckaers, A., & Lambrichts, I. (2016) · Wiley eBooks · doi:10.1002/9781118907474.ch25 · Cited by 1
Darinskas, A., Paskevicius, M., Apanavičius, G., Vilkevičius, G., Labanauskas, L., Ichim, T. E., & Rimdeika, R. (2020) · Journal of Translational Medicine · doi:10.1186/s12967-020-02266-3 · Cited by 1
RetractedRegenerative Medicine and the Diabetic Foot
Stern‐Buchbinder, Z. A., Hajhosseini, B., & Gurtner, G. C. (2020) · Wiley eBooks · doi:10.1002/9781119445821.ch28 · Cited by 1
Mesenchymal Stromal Cells in the Clinic: What Do the Clinical Trials Say?
Tanavde, V., & Vemuri, M. C. (2012) · Humana Press eBooks · doi:10.1007/978-1-62703-200-1_19
Cell-based therapy and rehabilitation with prosthetic limbs in a dog
Das, J., Nath, I., Routray, P., Rabindra Kumar, D. A. S., & Behera, S. S. (2015) · TURKISH JOURNAL OF VETERINARY AND ANIMAL SCIENCES · doi:10.3906/vet-1404-95
Self-citationNovel Cell-Based Therapies for the Treatment of Diabetic Ulceration
O’Loughlin, A. (2012) · Arrow@dit (Dublin Institute of Technology) · doi:10.13025/16518
Wound Healing Potential of Human Neonatal Mesenchymal Cells in an Animal Model of Hyperglycemia
Fouadi, M. (2012) · TSpace (University of Toronto)
Use of regenerative treatments in dermatology
Taşkın, B. (2016) · Istanbul Bilim University Florence Nightingale Transplantation Journal · doi:10.5606/fng.transplantasyon.2016.008
The role of mesenchymal stromal cells in the management of musculoskeletal disorders
Zwingenberger, S., Ojodu, I., Stiehler, M., & Goodman, S. B. (2016) · Wiley eBooks · doi:10.1002/9781118907474.ch47
The role of mesenchymal stem/stromal cells in the management of critical limb ischemia
Gupta, P., Chullikana, A., Sudha, B., Mathiazhagan, R., Raj, S. S., & Sen, M. A. (2016) · Wiley eBooks · doi:10.1002/9781118907474.ch46
Metadata
- Authors
- Dash, N. R., Dash, S. N., Routray, P., Mohapatra, S., & Mohapatra, P. C.
- Affiliations
- Sriram Chandra Bhanja Medical College Hospital (IN)
- Central Institute of Freshwater Aquaculture (IN)
- Corresponding author
- Mohapatra, Prakash C.
- Venue
- Rejuvenation Research
- Publisher
- SAGE Publications
- Published
- 2009-10
- Volume
- 12
- Issue
- 5
- Pages
- 359-366
- ISSN
- 1094-5458 (ISSN-L)
- 1549-1684
- 1557-8577
- OpenAlex
- W2018862422
- Cited by
- 339
- References
- 30
- Citations by year
- 2026: 11 · 2025: 11 · 2024: 19 · 2023: 23 · 2022: 35 · 2021: 19 · 2020: 21 · 2019: 17 · 2018: 33 · 2017: 25 · 2016: 20 · 2015: 19 · 2014: 14 · 2013: 27 · 2012: 26
- FWCI
- 15.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Rejuvenation Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Wound Healing and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetic Foot Ulcer Assessment and Management
- Keywords
- mesenchymal stem cells, bone marrow-derived stem cells, autologous cell therapy, chronic non-healing ulcers, diabetic foot ulcer, thromboangiitis obliterans, leg ulcers, wound healing, pain-free walking distance, stem cell transplantation, cell surface markers
- MeSH terms
- Adult, Biopsy, Humans, Inflammation, Leg, Male, Pain, Thromboangiitis Obliterans, Time Factors, Ulcer, Wound Healing, Foot Ulcer, Treatment Outcome, Lower Extremity, Mesenchymal Stem Cell Transplantation
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