Modulation of the Mesenchymal Stem Cell Secretome Using Computer-Controlled Bioreactors: Impact on Neuronal Cell Proliferation, Survival and Differentiation.
In recent years it has been shown that the therapeutic benefits of human mesenchymal stem/stromal cells (hMSCs) in the Central Nervous System (CNS) are mainly attributed to their secretome. The implementation of computer-controlled suspension bioreactors has shown to be a viable route for the expansion of these cells to large numbers. As hMSCs actively respond to their culture environment, there is the hypothesis that one can modulate its secretome through their use. Herein, we present data indicating that the use of computer-controlled suspension bioreactors enhanced the neuroregulatory profile of hMSCs secretome. Indeed, higher levels of in vitro neuronal differentiation and NOTCH1 expression in human neural progenitor cells (hNPCs) were observed when these cells were incubated with the secretome of dynamically cultured hMSCs. A similar trend was also observed in the hippocampal dentate gyrus (DG) of rat brains where, upon injection, an enhanced neuronal and astrocytic survival and differentiation, was observed. Proteomic analysis also revealed that the dynamic culturing of hMSCs increased the secretion of several neuroregulatory molecules and miRNAs present in hMSCs secretome. In summary, the appropriate use of dynamic culture conditions can represent an important asset for the development of future neuro-regenerative strategies involving the use of hMSCs secretome.
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|ICVS/3B's, PT Government Associate Lab, Braga/Guimarães, Portugal.
Fábio G
FG
Teixeira
Pharmaceutical Production Research Facility (PPRF), Schulich School of Engineering, University of Calgary, Calgary, Alberta, Canada.
Krishna M
KM
Panchalingam
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|ICVS/3B's, PT Government Associate Lab, Braga/Guimarães, Portugal.
Rita
R
Assunção-Silva
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|ICVS/3B's, PT Government Associate Lab, Braga/Guimarães, Portugal.
Sofia C
SC
Serra
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|ICVS/3B's, PT Government Associate Lab, Braga/Guimarães, Portugal.
Bárbara
B
Mendes-Pinheiro
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|ICVS/3B's, PT Government Associate Lab, Braga/Guimarães, Portugal.
Patrícia
P
Patrício
Pharmaceutical Production Research Facility (PPRF), Schulich School of Engineering, University of Calgary, Calgary, Alberta, Canada.
Sunghoon
S
Jung
CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal.|Faculty of Sciences and Technology, University of Coimbra, Portugal.
Sandra I
SI
Anjo
CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal.|Biocant - Biotechnology Innovation Center, Cantanhede, Portugal.
Bruno
B
Manadas
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|ICVS/3B's, PT Government Associate Lab, Braga/Guimarães, Portugal.
Luísa
L
Pinto
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|ICVS/3B's, PT Government Associate Lab, Braga/Guimarães, Portugal.
Nuno
N
Sousa
Pharmaceutical Production Research Facility (PPRF), Schulich School of Engineering, University of Calgary, Calgary, Alberta, Canada.
Leo A
LA
Behie
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|ICVS/3B's, PT Government Associate Lab, Braga/Guimarães, Portugal.
António J
AJ
Salgado
D000818:Animals; D019149:Bioreactors; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D003201:Computers; D006801:Humans; D007267:Injections; D008297:Male; D013058:Mass Spectrometry; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D017208:Rats, Wistar
D020543:Proteome