Secretome from Human Mesenchymal Stem Cells-Derived Endothelial Cells Promotes Wound Healing in a Type-2 Diabetes Mouse Model

Ormazabal, Valeska; Nova-Lampeti, Estefanía; Rojas, Daniela; Zúñiga, Felipe A.; Escudero, Carlos; Lagos, Paola; Moreno, Alexa; Pavez, Yanara; Reyes, Camila; Yáñez, Milly; Vidal, Mabel; Cabrera-Vives, Guillermo; Oporto, Katherine; Aguayo, Claudio

doi:10.3390/ijms23020941

Open AccessArticle

Secretome from Human Mesenchymal Stem Cells-Derived Endothelial Cells Promotes Wound Healing in a Type-2 Diabetes Mouse Model

by

Valeska Ormazabal

¹

,

Estefanía Nova-Lampeti

²

,

Daniela Rojas

³

,

Felipe A. Zúñiga

²

,

Carlos Escudero

^4,5

,

Paola Lagos

¹,

Alexa Moreno

²,

Yanara Pavez

²,

Camila Reyes

²,

Milly Yáñez

⁶,

Mabel Vidal

⁷

,

Guillermo Cabrera-Vives

⁷

,

Katherine Oporto

² and

Claudio Aguayo

^2,5,*

¹

Department of Pharmacology, Faculty of Biological Sciences, Universidad de Concepción, Concepción 4030000, Chile

²

Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, Universidad de Concepción, Concepción 4030000, Chile

³

Department of Animal Pathology, Faculty of Veterinary Sciences, Universidad de Concepción, Chillan 3787000, Chile

⁴

Vascular Physiology Laboratory, Department of Basic Sciences, Universidad del Bio-Bio, Chillan 3787000, Chile

⁵

Group of Research and Innovation in Vascular Health (GRIVAS Health), Chillan 3787000, Chile

⁶

Department of Pathological Anatomy, Las Higueras Hospital, Talcahuano 4030000, Chile

⁷

Department of Computer Science, Faculty of Engineering, Universidad de Concepción, Concepción 4030000, Chile

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2022, 23(2), 941; https://doi.org/10.3390/ijms23020941

Submission received: 15 September 2021 / Revised: 6 December 2021 / Accepted: 10 December 2021 / Published: 15 January 2022

(This article belongs to the Special Issue Advances in Stem Cell Research for Future Therapies and In Vitro Disease Modelling)

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Abstract

Tissue regeneration is often impaired in patients with metabolic disorders such as diabetes mellitus and obesity, exhibiting reduced wound repair and limited regeneration capacity. We and others have demonstrated that wound healing under normal metabolic conditions is potentiated by the secretome of human endothelial cell-differentiated mesenchymal stem cells (hMSC-EC). However, it is unknown whether this effect is sustained under hyperglycemic conditions. In this study, the wound healing effect of secretomes from undifferentiated human mesenchymal stem cells (hMSC) and hMSC-EC in a type-2 diabetes mouse model was analyzed. hMSC were isolated from human Wharton’s jelly and differentiated into hMSC-EC. hMSC and hMSC-EC secretomes were analyzed and their wound healing capacity in C57Bl/6J mice fed with control (CD) or high fat diet (HFD) was evaluated. Our results showed that hMSC-EC secretome enhanced endothelial cell proliferation and wound healing in vivo when compared with hMSC secretome. Five soluble proteins (angiopoietin-1, angiopoietin-2, Factor de crecimiento fibroblástico, Matrix metallopeptidase 9, and Vascular Endothelial Growth Factor) were enriched in hMSC-EC secretome in comparison to hMSC secretome. Thus, the five recombinant proteins were mixed, and their pro-healing property was evaluated in vitro and in vivo. Functional analysis demonstrated that a cocktail of these proteins enhanced the wound healing process similar to hMSC-EC secretome in HFD mice. Overall, our results show that hMSC-EC secretome or a combination of specific proteins enriched in the hMSC-EC secretome enhanced wound healing process under hyperglycemic conditions.

Keywords: human mesenchymal cells-derived endothelial cells; secretome; hyperglycemic conditions; regeneration

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MDPI and ACS Style

Ormazabal, V.; Nova-Lampeti, E.; Rojas, D.; Zúñiga, F.A.; Escudero, C.; Lagos, P.; Moreno, A.; Pavez, Y.; Reyes, C.; Yáñez, M.; et al. Secretome from Human Mesenchymal Stem Cells-Derived Endothelial Cells Promotes Wound Healing in a Type-2 Diabetes Mouse Model. Int. J. Mol. Sci. 2022, 23, 941. https://doi.org/10.3390/ijms23020941

AMA Style

Ormazabal V, Nova-Lampeti E, Rojas D, Zúñiga FA, Escudero C, Lagos P, Moreno A, Pavez Y, Reyes C, Yáñez M, et al. Secretome from Human Mesenchymal Stem Cells-Derived Endothelial Cells Promotes Wound Healing in a Type-2 Diabetes Mouse Model. International Journal of Molecular Sciences. 2022; 23(2):941. https://doi.org/10.3390/ijms23020941

Chicago/Turabian Style

Ormazabal, Valeska, Estefanía Nova-Lampeti, Daniela Rojas, Felipe A. Zúñiga, Carlos Escudero, Paola Lagos, Alexa Moreno, Yanara Pavez, Camila Reyes, Milly Yáñez, and et al. 2022. "Secretome from Human Mesenchymal Stem Cells-Derived Endothelial Cells Promotes Wound Healing in a Type-2 Diabetes Mouse Model" International Journal of Molecular Sciences 23, no. 2: 941. https://doi.org/10.3390/ijms23020941

APA Style

Ormazabal, V., Nova-Lampeti, E., Rojas, D., Zúñiga, F. A., Escudero, C., Lagos, P., Moreno, A., Pavez, Y., Reyes, C., Yáñez, M., Vidal, M., Cabrera-Vives, G., Oporto, K., & Aguayo, C. (2022). Secretome from Human Mesenchymal Stem Cells-Derived Endothelial Cells Promotes Wound Healing in a Type-2 Diabetes Mouse Model. International Journal of Molecular Sciences, 23(2), 941. https://doi.org/10.3390/ijms23020941

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Secretome from Human Mesenchymal Stem Cells-Derived Endothelial Cells Promotes Wound Healing in a Type-2 Diabetes Mouse Model

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