Nesrine Ebrahim1,2, Arigue A Dessouky3, Ola Mostafa1, Amira Hassouna4, Mohamed M Yousef1, Yasmin Seleem5, Eman Abd El Aziz M El Gebaly5, Mona M Allam6, Ayman Samir Farid7, Bayan A Saffaf8, Dina Sabry9,10, Ahmed Nawar11, Ahmed A Shoulah11, Ahmed H Khalil12, Sami F Abdalla13, Mohamed El-Sherbiny14,15, Nehal M Elsherbiny16,17, Rabab F Salim18. 1. Department of Histology and Cell Biology Faculty of Medicine, Benha University, Benha, Egypt. 2. Stem Cell Unit, Faculty of Medicine, Benha University, Benha, Egypt. 3. Department of Histology and Cell Biology, Faculty of Medicine, Zagazig University, Zagazig, Egypt. 4. School of Interprofessional Health Studies, Faculty of Health and Environmental Sciences, AUT University, Auckland, New Zealand. 5. Department of Clinical Pharmacology, Faculty of Medicine, Benha University, Benha, Egypt. 6. Department of Medical Physiology, Faculty of Medicine, Benha University, Benha, Egypt. 7. Department of Clinical Pathology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh, Qalyubia, 13736, Egypt. 8. Department of Pharmacology, Faculty of Pharmacy, Future University, New Cairo, Egypt. 9. Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt. 10. Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Badr University, Cairo, 11562, Egypt. 11. Department of General Surgery, Faculty of Medicine, Benha University, Benha, Egypt. 12. Department of Surgery, & Radiology Faculty of Veterinary Medicine, Benha University, Benha, Egypt. 13. Clinical Department, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia. 14. Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia. 15. Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 16. Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt. drnehal@hotmail.com. 17. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia. drnehal@hotmail.com. 18. Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Benha University, Benha, Egypt. rabab.bio@yahoo.com.
Abstract
BACKGROUND: Diabetic foot ulceration is a serious chronic complication of diabetes mellitus characterized by high disability, mortality, and morbidity. Platelet-rich plasma (PRP) has been widely used for diabetic wound healing due to its high content of growth factors. However, its application is limited due to the rapid degradation of growth factors. The present study aimed to evaluate the efficacy of combined adipose-derived mesenchymal stem cells (ADSCs) and PRP therapy in promoting diabetic wound healing in relation to the Notch signaling pathway. METHODS: Albino rats were allocated into 6 groups [control (unwounded), sham (wounded but non-diabetic), diabetic, PRP-treated, ADSC-treated, and PRP+ADSCs-treated groups]. The effect of individual and combined therapy was evaluated by assessing wound closure rate, epidermal thickness, dermal collagen, and angiogenesis. Moreover, gene and protein expression of key elements of the Notch signaling pathway (Notch1, Delta-like canonical Notch ligand 4 (DLL4), Hairy Enhancer of Split-1 (Hes1), Hey1, Jagged-1), gene expression of angiogenic marker (vascular endothelial growth factor and stromal cell-derived factor 1) and epidermal stem cells (EPSCs) related gene (ß1 Integrin) were assessed. RESULTS: Our data showed better wound healing of PRP+ADSCs compared to their individual use after 7 and 14 days as the combined therapy caused reepithelialization and granulation tissue formation with a marked increase in area percentage of collagen, epidermal thickness, and angiogenesis. Moreover, Notch signaling was significantly downregulated, and EPSC proliferation and recruitment were enhanced compared to other treated groups and diabetic groups. CONCLUSIONS: These data demonstrated that PRP and ADSCs combined therapy significantly accelerated healing of diabetic wounds induced experimentally in rats via modulating the Notch pathway, promoting angiogenesis and EPSC proliferation.
BACKGROUND:Diabetic foot ulceration is a serious chronic complication of diabetes mellitus characterized by high disability, mortality, and morbidity. Platelet-rich plasma (PRP) has been widely used for diabetic wound healing due to its high content of growth factors. However, its application is limited due to the rapid degradation of growth factors. The present study aimed to evaluate the efficacy of combined adipose-derived mesenchymal stem cells (ADSCs) and PRP therapy in promoting diabetic wound healing in relation to the Notch signaling pathway. METHODS: Albino rats were allocated into 6 groups [control (unwounded), sham (wounded but non-diabetic), diabetic, PRP-treated, ADSC-treated, and PRP+ADSCs-treated groups]. The effect of individual and combined therapy was evaluated by assessing wound closure rate, epidermal thickness, dermal collagen, and angiogenesis. Moreover, gene and protein expression of key elements of the Notch signaling pathway (Notch1, Delta-like canonical Notch ligand 4 (DLL4), Hairy Enhancer of Split-1 (Hes1), Hey1, Jagged-1), gene expression of angiogenic marker (vascular endothelial growth factor and stromal cell-derived factor 1) and epidermal stem cells (EPSCs) related gene (ß1 Integrin) were assessed. RESULTS: Our data showed better wound healing of PRP+ADSCs compared to their individual use after 7 and 14 days as the combined therapy caused reepithelialization and granulation tissue formation with a marked increase in area percentage of collagen, epidermal thickness, and angiogenesis. Moreover, Notch signaling was significantly downregulated, and EPSC proliferation and recruitment were enhanced compared to other treated groups and diabetic groups. CONCLUSIONS: These data demonstrated that PRP and ADSCs combined therapy significantly accelerated healing of diabetic wounds induced experimentally in rats via modulating the Notch pathway, promoting angiogenesis and EPSC proliferation.
Authors: Serena Rubina Baglio; Koos Rooijers; Danijela Koppers-Lalic; Frederik J Verweij; M Pérez Lanzón; Nicoletta Zini; Benno Naaijkens; Francesca Perut; Hans W M Niessen; Nicola Baldini; D Michiel Pegtel Journal: Stem Cell Res Ther Date: 2015-07-01 Impact factor: 6.832