Regenerative medicine in the care of diabetic foot ulcers. A Systematic Review.
Abstract
Introduction: The pluripotency of stem cells (SC) and platelet-rich plasma (PRP) makes them potential candidates to accelerate tissue repair processes in lesions such as diabetic foot ulcers (DFU).
Objective: To evaluate the current evidence on the benefits of healing DFUs that do not respond to conventional treatment with SC and/or PRP.
Method: Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we systematically review original studies published in the last 5 years and indexed in Web of Science, Scopus, CUIDEN, and PubMed to evaluate the effects of SC and/or PRP on skin markers, healing time and adverse effects in DFU. The study was registered in PROSPERO (#CRD 42024537847).
Results: Among 107 records identified in the search, 5 studies met the inclusion criteria. DFUs treated with topically administered PRP or intralesional injection achieved a significant (p < 0.05) reduction in ulcer/ wound area. The overall cure rate improved significantly (p < 0.05) after the application of SC. Treatment with SC was able to reduce the amputation rate non-significantly (p > 0.05). The epithelialization or healing processes did not experience significant changes (p > 0.05) after the use of PRP or SC. No serious adverse effects were reported.
Conclusion: Cell therapy with SC and/or PRP on DFUs that do not heal with conventional treatment is a safe and effective therapeutic option.
Downloads
-
Abstract290
-
ESP_PDF (Español (España))161
-
ENG_PDF50
-
XML (Español (España))0
References
Banday MZ, Sameer AS, Nissar S. Pathophysiology of diabetes: An overview. Avicenna J Med Int. 2020;10(4):174-188. doi:10.4103/AJM.AJM_53_20.ç
World Health Organization. Diabetes Available at: https://www.who.int/es/news-room/fact-sheets/detail/diabetes (Access 25 January 2025).
International Diabetes Federation Facts and figures about diabetes Available at: https://idf.org/es/about-diabetes/diabetes-facts-figures/ (Access 25 January 2025).
Sociedad Española de Diabetes Prevalencia de diabetes de Europa Available at: https://www.sediabetes.org/comunicacion/sala-de-prensa/espana-es-el-segundo-pais-con-mayor-prevalencia-de-diabetes-de-europa/ (Access 25 January 2025).
Syauta D, Mulawardi, Prihantono, Hendarto J, Mariana N, Sulmiati, et al. Risk factors affecting the degree of diabetic foot ulcers according to Wagner classification in diabetic foot patients. Med Clínica Práctica. 2021;4: 100231. doi:10.1016/J.MCPSP.2021.100231.
Ahmeti I, Bogoev M, Petrovski G, Milenkovic T, Krstevska B, Taravari A. Influence of metabolic dysregulation in pre ulcerative phase of diabetic foot. J Diabet Foot Complicat. 2012;4(2):6–12.
Wang X, Yuan CX, Xu B, Yu Z. Diabetic foot ulcers: Classification, risk factors and management. World J Diabetes. 2022;13(12):1049. doi:10.4239/WJD.V13.I12.1049.
Elsayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, et al. 2. Classification and Diagnosis of Diabetes: Standards of Care in Diabetes-2023. Diabetes Care. 2023;46(Suppl 1):S19–40. doi:10.2337/DC23-S002.
Lavery LA, Suludere MA, Attinger CE, Malone M, Kang GE, Crisologo PA, et al. WHS (Wound Healing Society) guidelines update: Diabetic foot ulcer treatment guidelines. Wound Repair Regen. 2024;32(1):34–46. doi:10.1111/WRR.13133.
Okonkwo UA, Dipietro LA. Diabetes and Wound Angiogenesis. Int J Mol Sci. 2017;18(7):1419. doi:10.3390/IJMS18071419.
Brem H, Tomic-Canic M. Cellular and molecular basis of wound healing in diabetes. J Clin Invest. 2007;117(5):1219–1222. doi:10.1172/JCI32169.
Guo S, DiPietro LA. Factors Affecting Wound Healing. J Dent Res [Internet]. Maart 2010 [cited 27 April 2024];89(3):219. Available at: /pmc/articles/PMC2903966/
Han G, Ceilley R. Chronic Wound Healing: A Review of Current Management and Treatments. Adv Ther. 2017;34(3):599–610. doi:10.1007/S12325-017-0478-Y.
Rodríguez GJ, Córdoba-Doña JA, Escolar-Pujolar A, Aguilar-Diosdado M, Goicolea I. Familia, economía y servicios sanitarios: claves de los cuidados en pacientes con diabetes y amputación de miembros inferiores. Estudio cualitativo en Andalucía. Aten Primaria. 2018;50(10):611-620. doi:10.1016/J.APRIM.2017.06.011.
Reddy SHR, Reddy R, Babu NC, Ashok GN. Stem-cell therapy and platelet-rich plasma in regenerative medicines: A review on pros and cons of the technologies. J Oral Maxillofac Pathol. 2018;22(3):367-374. doi:10.4103/JOMFP.JOMFP_93_18.
Martinez-Zapata MJ, Martí-Carvajal AJ, Solà I, Expósito JA, Bolíbar I, Rodríguez L, et al. Autologous platelet-rich plasma for treating chronic wounds. Cochrane Database Syst Rev. 2016(5):CD006899. doi:10.1002/14651858.cd006899.pub2.
Rodríguez Valiente M, García Hernández AM, Almansa Saura S, Bernabé García Á, Blanquer M, Liarte Lastra SD, et al. Terapia celular con membrana amniótica para la epitelización de úlceras complejas de pie diabético. Enfermería Dermatológica. 2020;14(39):36–43. doi:10.5281/zenodo.3780037.
Ivanova Y, Gramatiuk S, Kryvoruchko I, Tymchenko M, Goltsev K, Sargsyan K. Investigating the joint application of negative pressure wound treatment and tissue therapy for chronic wounds in patients with diabetes. J Med Life. 2023;16(7):1098–1104. doi:10.25122/JML-2023-0020.
An T, Chen Y, Tu Y, Lin P. Mesenchymal Stromal Cell-Derived Extracellular Vesicles in the Treatment of Diabetic Foot Ulcers: Application and Challenges. Stem cell Rev reports. 2021;17(2):369–378.
Hetta HF, Elsaghir A, Sijercic VC, Akhtar MS, Gad SA, Moses A, et al. Mesenchymal stem cell therapy in diabetic foot ulcer: An updated comprehensive review. Heal Sci reports. 2024;7(4):e2036. doi:10.1002/HSR2.2036.
Teraa M, Conte MS, Moll FL, Verhaar MC. Critical Limb Ischemia: Current Trends and Future Directions. J Am Heart Assoc. 2016;5(2):e002938. doi:10.1161/JAHA.115.002938.
Delcogliano M, Sangiorgio A, Bensa A, Andriolo L, Boffa A, Filardo G. Platelet-rich plasma augmentation in anterior cruciate ligament reconstruction: Evidence is still too scattered. A scoping review of randomised controlled trials. Knee Surg Sports Traumatol Arthrosc. 2024;32(5): 1143-1159. doi:10.1002/KSA.12127.
Dizdar SK, Doğan U, Ece M, Kaya KS, Seyhun N, Turgut S. Effects of submucoperichondrial application of platelet-rich plasma on nasal mucosal healing after septoplasty. Auris Nasus Larynx. 2024;51(3):437–442. doi:10.1016/J.ANL.2023.12.003.
Bava ED, Barber FA. Platelet-rich plasma products in sports medicine. Phys Sportsmed. 2011;39(3):94–99. doi:10.3810/psm.2011.09.1925.
Gentile P, Calabrese C, De Angelis B, Dionisi L, Pizzicannella J, Kothari A, et al. Impact of the Different Preparation Methods to Obtain Autologous Non-Activated Platelet-Rich Plasma (A-PRP) and Activated Platelet-Rich Plasma (AA-PRP) in Plastic Surgery: Wound Healing and Hair Regrowth Evaluation. Int J Mol Sci. 2020;21(2):431. doi:10.3390/IJMS21020431.
Salazar-Álvarez AE, Riera-del-Moral LF, García-Arranz M, Álvarez-García J, Concepción-Rodriguez NA, Riera-de-Cubas L. Uso de plasma rico en plaquetas para cicatrización de úlceras crónicas de miembros inferiores. Actas Dermosifiliogr. 2014;105(6):597–604. doi:10.1016/J.AD.2013.12.011.
Conde Montero E, Fernández Santos ME, Suárez Fernández R. Plasma rico en plaquetas: aplicaciones en dermatología. Actas Dermosifiliogr. 2015;106(2):104–111. doi:10.1016/J.AD.2013.12.021.
Lynch SE, Nixon JC, Colvin RB, Antoniades HN. Role of platelet-derived growth factor in wound healing: synergistic effects with other growth factors. Proc Natl Acad Sci. 1987;84(21):7696–7700. doi:10.1073/PNAS.84.21.7696.
Bhatnagar P, Law JX, Ng SF. Delivery systems for platelet derived growth factors in wound healing: A review of recent developments and global patent landscape. J Drug Deliv Sci Technol. 2022;71:103270. doi:10.1016/J.JDDST.2022.103270.
Scopelliti F, Cattani C, Dimartino V, Mirisola C, Cavani A. Platelet Derivatives and the Immunomodulation of Wound Healing. Int J Mol Sci. 2022;23(15):8370. doi:10.3390/IJMS23158370.
An T, Chen Y, Tu Y, Lin P. Mesenchymal Stromal Cell-Derived Extracellular Vesicles in the Treatment of Diabetic Foot Ulcers: Application and Challenges. Stem cell Rev reports. 2021;17(2):369–378. doi:10.1007/S12015-020-10014-9.
Kirana S, Stratmann B, Prante C, Prohaska W, Koerperich H, Lammers D, et al. Autologous stem cell therapy in the treatment of limb ischaemia induced chronic tissue ulcers of diabetic foot patients. Int J Clin Pract. 2012;66(4):384–393. doi:10.1111/J.1742-1241.2011.02886.X.
Procházka V, Gumulec J, Jalůvka F, Šalounová D, Jonszta T, Czerný D, et al. Cell therapy, a new standard in management of chronic critical limb ischemia and foot ulcer. Cell Transplant. 2010;19(11):1413–1424. doi:10.3727/096368910X514170.
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Rev Esp Cardiol (Engl Ed). 2021;74(9):790–799. doi:10.1016/J.REC.2021.07.010.
Bibloteca virtual de salud. DeCS – Descritores en Ciencias de la Salud. [cited 28 April 2025]. Available at: https://decs.bvsalud.org/es/
National Library of medicine (NIH). Medical Subject Headings. [cited 28 April 2025]. Available at: https://www.nlm.nih.gov/mesh/meshhome.html
Brown P, Brunnhuber K, Chalkidou K, Chalmers I, Clarke M, Fenton M, et al. Health research: How to formulate research recommendations. BMJ Br Med J. 2006;333(7572):804-806. doi:10.1136/BMJ.38987.492014.94.
Law M, Stewart D, Letts L, Pollock N, Bosch J WM. Guidelines for Critical Review of Qualitative Studies; McMaster University Occupational Therapy Evidence-Based Practice Research Group: Hamilton, ON, Canada, 1998.
Smith OJ, Leigh R, Kanapathy M, Macneal P, Jell G, Hachach-Haram N, et al. Fat grafting and platelet-rich plasma for the treatment of diabetic foot ulcers: A feasibility-randomised controlled trial. Int Wound J. 2020;17(6):1578–1594. doi:10.1111/IWJ.13433.
Orellano P, Torres Negreira M, Colombo A, Lamela N, Saliwonczyk D, Berro M, et al. Experiencia con el uso de plasma rico en plaquetas autólogo en el tratamiento de las úlceras del pie diabético. Rev Médica del Uruguay. 2021;37(3):e37302. doi:10.29193/RMU.37.3.1.
Lu D, Jiang Y, Deng W, Zhang Y, Liang Z, Wu Q, et al. Long-Term Outcomes of BMMSC Compared with BMMNC for Treatment of CriticalLimb Ischemia and Foot Ulcer in Patients with Diabetes. Cell Transplant. 2019;28(5):645-652. doi:10.1177/0963689719835177.
De la Torre Barbero M jose, Luna MJE, Moreno JR. Uso del Plasma Rico en Plaquetas para el tratamiento de las úlceras de miembro inferior. Estudio piloto. Rev Enfermería Vasc. 2020;3(6):15–21. doi:10.35999/rdev.v3i6.77.
Askø Andersen J, Rasmussen A, Frimodt-Møller M, Engberg S, Steeneveld E, Kirketerp-Møller K, et al. Novel topical allogeneic bone-marrow-derived mesenchymal stem cell treatment of hard-to-heal diabetic foot ulcers: a proof of concept study. Stem Cell Res Ther. 2022;13(1):280. doi:10.1186/S13287-022-02951-8.
OuYang H, Tang Y, Yang F, Ren X, Yang J, Cao H, et al. Platelet-rich plasma for the treatment of diabetic foot ulcer: a systematic review. Front Endocrinol (Lausanne). 2023;14: 1256081. doi:10.3389/FENDO.2023.1256081.
Babaei V, Afradi H, Gohardani HZ, Nasseri F, Azarafza M, Teimourian S. Management of chronic diabetic foot ulcers using platelet-rich plasma. J Wound Care. 2017;26(12):784–787. doi:10.12968/JOWC.2017.26.12.784.
Picard F, Hersant B, Bosc R, Meningaud JP. The growing evidence for the use of platelet-rich plasma on diabetic chronic wounds: A review and a proposal for a new standard care. Wound Repair Regen. 2015;23(5):638–643. doi:10.1111/WRR.12317.
Ahmed M, Reffat SA, Hassan A, Eskander F. Platelet-Rich Plasma for the Treatment of Clean Diabetic Foot Ulcers. Ann Vasc Surg. 2017;38:206–211. doi:10.1016/J.AVSG.2016.04.023.
Mimeault M, Hauke R, Batra SK. Stem cells: a revolution in therapeutics-recent advances in stem cell biology and their therapeutic applications in regenerative medicine and cancer therapies. Clin Pharmacol Ther. 2007;82(3):252–264. doi:10.1038/SJ.CLPT.6100301.
Wu Q, Chen B, Liang Z. Mesenchymal Stem Cells as a Prospective Therapy for the Diabetic Foot. Stem Cells Int. 2016; 2016:4612167. doi:10.1155/2016/4612167.
Iwase T, Nagaya N, Fujii T, Itoh T, Murakami S, Matsumoto T, et al. Comparison of angiogenic potency between mesenchymal stem cells and mononuclear cells in a rat model of hindlimb ischemia. Cardiovasc Res. 2005;66(3):543–551. doi:10.1016/J.CARDIORES.2005.02.006.
Muñoz M, Vásquez B, Sol M del. Molecular Mechanisms in the Process of Re-epithelization in Wound Healing and the Action of Honey in Keratinocytes. Int J Morphol 2020;38(6):1700–1706.
Stojadinovic O, Pastar I, Vukelic S, Mahoney MG, Brennan D, Krzyzanowska A, et al. Deregulation of keratinocyte differentiation and activation: a hallmark of venous ulcers. J Cell Mol Med. 2008;12(6B):2675–2690. doi:10.1111/J.1582-4934.2008.00321.X.
Alonso Castellanos S, Soto Célix M, Alonso Galarreta J, del Riego Valledor A, de la Torre AM. Efectos adversos metabólicos y nutricionales asociados a la terapia biológica del cáncer. Nutr Hosp. 2014;29(2):259–268. doi:10.3305/NH.2014.29.2.7023.
Maseda Pedrero R. Estudio de seguridad y eficacia preliminar de la infusión de células madre mesenquimales haploidénticas derivadas de médula ósea para el tratamiento de la epidermólisis bullosa distrófica recesiva. Tesis Doctoral. Madrid. Universidad Autónoma de Madrid. Available at: https://dialnet.unirioja.es/servlet/tesis?codigo=305553&info=resumen&idioma=SPA
Copyright (c) 2025 Global Nursing

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
The works published in this magazine are subject to the following terms:
1. The Publications Service of the University of Murcia (the publisher) preserves the copyright of the published works, and encourages and allows the reuse of the works under the license for use stated in point 2.
© Servicio de Publicaciones, Universidad de Murcia, 2011 (© Publications Service, University of Murcia, 2011)
2. The works are published in the electronic edition of the journal under Creative Commons Reconocimiento-NoComercial-SinObraDerivada 3.0 España(texto legal) “ a Attribution-NonCommercial-NoDerivatives 3.0 Spain license (legal text)”. They can be copied, used, broadcasted, transmitted and publicly displayed, provided that: i) the authorship and original source of their publication (journal, publisher and URL) are cited; (ii) are not used for commercial purposes; iii) the existence and specifications of this license is mentioned.
3. Conditions of self-archiving. Authors are allowed and encouraged to electronically disseminate the pre-print (pre-reviewed ) and / or post-print (reviewed and accepted for publication) versions of their works prior to publication, as it ensures a wider circulation and dissemination which may lead to a possible increase in its mention and a higher scope among the academic community. RoMEO color: green.










