Feline bone marrow-derived mesenchymal stem cells express several pluripotent and neural markers and easily turn into neural-like cells by manipulation with chromatin modifying agents and neural inducing factors. Cell Reprogram 2011 Oct;13(5):385-90
Date
07/02/2011Pubmed ID
21718099DOI
10.1089/cell.2011.0007Scopus ID
2-s2.0-80053554317 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
Recent studies suggest that cellular therapies that utilize mesenchymal stem cells (MSCs), especially ones that have been neurally induced (NI), may provide a functional benefit in a wide range of neurological disorders. Recently, we developed a new method for the efficient generation of neural cells from human bone marrow (BM)-derived MSCs (hMSC). Neural induction was achieved by exposing cells simultaneously to chromatin-modifying agents and neural-inducing factors. When transplanted into injured spinal cords, these NI-hMSCs survived, differentiated, promoted tissue preservation, and significantly improved locomotor recovery of injured animals. In the current study, we sought to determine whether this methodological approach would be equally effective in generating neural-like cells from feline BM-derived MSCs (fMSC). Our long-term goal is to develop an autologous source of neural stem cells that can be used in cellular replacement therapies in large animal (feline) models of neurological disorders. Our results showed that fMSCs exhibited a neural morphology after 48-72 h of neural induction. Immunocytochemistry, ELISA, Western blot, and real-time RT-PCR studies revealed a higher level of expression of several pluripotent and neural genes in NI-fMSCs, the majority of which were expressed in untreated fMSCs at relatively low levels. We concluded that the expression of pluripotency- and neural-associated genes in unmodified fMSCs make them more pliable for reprogramming into a neural fate by manipulation with chromatin modifying agents and neural inducing factors.
Author List
Zhang Z, Maiman DJ, Kurpad SN, Crowe MJ, Alexanian ARAuthors
Arshak R. Alexanian VMD, PhD Adjunct Associate Professor in the Medicine department at Medical College of WisconsinShekar N. Kurpad MD, PhD Chair, Director, Professor in the Neurosurgery department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsAntigens, Differentiation
Bone Marrow Cells
Cats
Cell Survival
Cells, Cultured
Chromatin
Enzyme Inhibitors
Humans
Neural Stem Cells
Pluripotent Stem Cells
Spinal Cord Injuries
Transplantation, Autologous