The contribution of probiotics to combined cellular therapy in skin wound healing in diabetic rats

Sep 30, 2026

Diabetes-related wound care remains a major clinical challenge because chronic, non-healing ulcers are vulnerable to infection and can progress to amputation. Experimental evidence is limited on whether probiotics enhance combined cellular therapy. This study evaluates probiotics as an oral adjunct to a triple cellular approach using mesenchymal stem cells, stromal vascular fraction, and platelet-rich plasma in a streptozotocin-induced diabetic rat model, assessing histology, immunomarkers, and microbiome changes.

LanguageEnglish

CategoryResearch & Report

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Pages12

Reading Time30 min

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Abstract

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EXPERIMENTAL STUDY The contribution of probiotics to combined cellular therapy in skin wound healing in diabetic rats Emine Müge Karakayalı,1 İbrahim Tuğlu2 1Department of Medical Microbiology, Izmir Democracy University Faculty of Medicine, İzmir-Türkiye 2Department of Histology and Embryology, Manisa Celal Bayar University Faculty of Medicine, Manisa-Türkiye ABSTRACT BACKGROUND: Diabetes-related wound care is still a major issue due to chronic and hon-healing ulcers that are prone to infection and ultimately amputation. In recent years, cellular therapy (CT) products such as mesenchymal stem cells (MSC), platelet-rich plasma (PRP), and stromal vascular fraction (SVF) have been widely used. A combined cellular therapy (CCT) has not yet been tested as a triple combination, although its use alone and in dual combinations has been investigated. Probiotics (PB) accelerate healing by altering the intestinal microbiota. This study aims to examine the role of PB in enhancing the effects of CCT on diabetic wound healing. METHODS: A 1×1 cm2 full-thickness cutaneous wound was created after administering 40 mg/kg streptozotocin intraperitoneally (STZ i.p.) to induce a diabetic (DB) animal model. Animals were divided into four groups: DB, DB+PB, DB+CCT, and DB+CCT+PB, each with six adult Albino rats. The wound edges were treated with a total of 300 µL of solution, consisting of 30 µL each of 100 µL 1×106 MSC, 100 µL SVF, and 100 µL PRP as CCT. PB was administered orally at a dose of approximately 200 mg daily. Histochemical analyses were performed using hematoxylin and eosin (HE) and Masson’s trichrome (MT). Immunohistochemical analyses were conducted for endothelial nitric oxide synthase (eNOS), Caspase-3, interleukin-10 (IL-10), vascular endothelial growth factor (VEGF), and Collagen I. The intestinal microbiome was examined through metagenomic analyses of taxonomic structure. RESULTS: Combined cellular therapy provided more effective and faster healing in DB animals. It was discovered that PB further accelerated this process, leading to greater improvement. CCT was observed to reverse high eNOS, Caspase-3, and IL-10 expression, as well as low VEGF and Collagen I levels. Moreover, PB therapy significantly enhanced the positive effects of CCT. CCT in combination with PB significantly improved wound healing by preventing oxidative stress, apoptosis, and inflammation, while promoting vascularization and collagen organization. CONCLUSION: Probiotic support was considered important for diabetic wound healing and was suggested to improve patients’quality of life. Keywords: Cell therapy; diabetic skin; rat; probiotics; wound healing. INTRODUCTION Diabetes-related wound ulcers are slow-healing and costly complications characterized by impaired vascularization, inflammation, oxidative stress, apoptosis, and reduced signaling that are important for healing. Mesenchymal stem cells (MSC), platelet-rich plasma (PRP), and stromal vascular fraction (SVF) are frequently used to treat these disorders, providing an effective therapeutic strategy. Mesenchymal stem cells are vital for treatment due to the cellular support they provide, the growth factors they release, and the regenerative environment they create.[1] PRP has gained popularity in recent years, both for its growth factors and for the support it offers to MSC. SVF is widely used in | Cite this article as: Karakayalı EM, Tuğlu İ. The contribution of probiotics to cellular therapy in skin wound healing in diabetic rats. Ulus Travma Acil Cerrahi Derg 2025;31:925-936.
Address for correspondence: Emine Müge Karakayalı
Department of Medical Microbiology, Izmir Democracy University Faculty of Medicine, İzmir, Türkiye [E-mail: mituglu@yahoo.com](E-mail: mituglu@yahoo.com) | | | --- | --- | | Ulus Travma Acil Cerrahi Derg 2025;31(10):925-936 DOI: 10.14744/tjtes.2025.37711
Submitted: 28.02.2025 Revised: 05.08.2025 Accepted: 29.08.2025 Published: 07.10.2025
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FAQs

What problem does the study address in diabetic wound care?

The study targets slow, non-healing diabetic skin ulcers that are associated with impaired vascularization, inflammation, oxidative stress, apoptosis, and infection risk.

How were probiotics administered and how did they relate to the treatment groups?

Probiotics were given orally at about 200 mg daily, and animals were grouped into diabetic alone, diabetic plus probiotics, diabetic plus combined cellular therapy, and diabetic plus combined cellular therapy plus probiotics.

What improvements were observed when probiotics were added to combined cellular therapy?

Combined cellular therapy improved healing, and probiotic supplementation further accelerated recovery while improving molecular and histochemical markers linked to oxidative stress, apoptosis, inflammation, vascularization, and collagen organization.

Sep 30, 2026

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