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Abstract
IntroductionThe use of human umbilical cord Wharton Jelly-derived mesenchymal stem cells (hWJ-MSCs) has been considered a new potential source for future safe applications in regenerative medicine. Indeed, the application of hWJ-MSCs into different animal models of disease, including those from the central nervous system, has shown remarkable therapeutic benefits mostly associated with their secretome. Conventionally, hWJ-MSCs are cultured and characterized under normoxic conditions (21 % oxygen tension), although the oxygen levels within tissues are typically much lower (hypoxic) than these standard culture conditions. Therefore, oxygen tension represents an important environmental factor that may affect the performance of mesenchymal stem cells in vivo. However, the impact of hypoxic conditions on distinct mesenchymal stem cell characteristics, such as the secretome, still remains unclear.MethodsIn the present study, we have examined the effects of normoxic (21 % O2) and hypoxic (5 % O2) conditions on the hWJ-MSC secretome. Subsequently, we address the impact of the distinct secretome in the neuronal cell survival and differentiation of human neural progenitor cells.ResultsThe present data indicate that the hWJ-MSC secretome collected from normoxic and hypoxic conditions displayed similar effects in supporting neuronal differentiation of human neural progenitor cells in vitro. However, proteomic analysis revealed that the use of hypoxic preconditioning led to the upregulation of several proteins within the hWJ-MSC secretome.ConclusionsOur results suggest that the optimization of parameters such as hypoxia may lead to the development of strategies that enhance the therapeutic effects of the secretome for future regenerative medicine studies and applications.
Highlights
The use of human umbilical cord Wharton Jelly-derived mesenchymal stem cells has been considered a new potential source for future safe applications in regenerative medicine
Our results suggest that the optimization of parameters such as hypoxia may lead to the development of strategies that enhance the therapeutic effects of the secretome for future regenerative medicine studies and applications
The bioreactors were maintained at: (1) 37 °C using a heating jacket; (2) 100 % dissolved oxygen for normoxic conditions; (3) 21 % dissolved oxygen for hypoxic conditions; (4) pH of 7.4, controlled by a gas mixture connected to oxygen, nitrogen, carbon dioxide and air tanks that was introduced into the headspace; and (5) agitation of 52 rpm using a magnetic stir plate under the bioreactors
Summary
The use of human umbilical cord Wharton Jelly-derived mesenchymal stem cells (hWJ-MSCs) has been considered a new potential source for future safe applications in regenerative medicine. The application of hWJ-MSCs into different animal models of disease, including those from the central nervous system, has shown remarkable therapeutic benefits mostly associated with their secretome. The use of adult stem cells, including human mesenchymal stem cells (hMSCs), as a possible therapeutic tool in the regenerative medicine field has been widely assessed [1,2,3], and has emerged as a promising therapeutic approach [4,5,6]. Over the last decade, there has been a substantial effort to assess the impact of MSCs (including hWJ-MSCs) and their secretome into different disorders, such as those affecting the central nervous system (CNS) [14]. Despite promising results for hMSCs and their paracrine activity, the low number of cells that are normally obtained after isolation continues to be a limitation for their
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