Acellular Biomaterials Associated with Autologous Bone Marrow-Derived Mononuclear Stem Cells Improve Wound Healing through Paracrine Effects

Author:

de Souza Isio Carvalho1,Takejima Aline Luri1,Simeoni Rossana Baggio1,Gamba Luize Kremer1,Ribeiro Victoria Stadler Tasca1ORCID,Foltz Katia Martins1ORCID,de Noronha Lucia1,de Almeida Meila Bastos2,Neto Jose Rocha Faria1,de Carvalho Katherine Athayde Teixeira3ORCID,da Silveira Paulo Cesar Lock4,Pinho Ricardo Aurino5ORCID,Francisco Julio Cesar1ORCID,Guarita-Souza Luiz César1ORCID

Affiliation:

1. Experimental Laboratory of Institute of Biological and Health Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), 1555 Imaculada Conceição Street, Curitiba 80215-901, SP, Brazil

2. Department of Veterinary Medicine, Universidade Federal do Paraná (UFPR), Rua XV de Novembro, 1299, Curitiba 80060-000, SP, Brazil

3. Cell Therapy and Biotechnology in Regenerative Medicine Department, The Pelé Pequeno Príncipe Institute, Child and Adolescent Health Research & Pequeno Príncipe Faculties, 1632 Silva Jardim Avenue, Curitiba 80240-902, SP, Brazil

4. Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma 88806-000, SC, Brazil

5. Laboratory of Exercise Biochemistry in Health, School of Medicine, Graduate Program in Health Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), 1555 Imaculada Conceição Street, Curitiba 80215-901, SP, Brazil

Abstract

Wound healing is a complex process of repair that involves the interaction between different cell types and involves coordinated interactions between intracellular and extracellular signaling. Bone Marrow Mesenchymal Stem Cells (BMSCs) based and acellular amniotic membrane (AM) therapeutic strategies with the potential for treatment and regeneration of tissue. We aimed to evaluate the involvement of paracrine effects in tissue repair after the flap skin lesion rat model. In the full-thickness flap skin experiment of forty Wistar rats: A total of 40 male Wistar rats were randomized into four groups: group I: control (C; n = 10), with full-thickness lesions on the back, without (BMSCs) or AM (n = 10); group II: injected (BMSCs; n = 10); group III: covered by AM; group IV–injected (AM + BMSCs; n = 10). Cytokine levels, IL-1, and IL-10 assay kits, superoxide dismutase (SOD), glutathione reductase (GRs) and carbonyl activity levels were measured by ELISA 28th day, and TGF-β was evaluated by immunohistochemical, the expression collagen expression was evaluated by Picrosirius staining. Our results showed that the IL-1 interleukin was higher in the control group, and the IL-10 presented a higher mean when compared to the control group. The groups with BMSCs and AM showed the lowest expression levels of TGF-β. SOD, GRs, and carbonyl activity analysis showed a predominance in groups that received treatment from 80%. The collagen fiber type I was predominant in all groups; however, the AM + BMSCs group obtained a higher average when compared to the control group. Our findings suggest that the AM+ BMSCs promote skin wound healing, probably owing to their paracrine effect attributed to the promotion of new collagen for tissue repair.

Funder

Coordination for the Improvement of Higher Education Personnel

National Council for Scientific

Technological Development

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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