Affiliations: Biomolecular Science Institute, University of Central
Florida, Orlando, FL 32816, USA | Department of Psychiatry, University of Illinois at
Chicago, Chicago, IL 60612, USA | Department of Ophthalmology and Visual Sciences,
University of Illinois at Chicago, Chicago, IL 60612, USA
Abstract: Purpose: Recent reports show that marrow derived mesenchymal stem
cells (MeSCs) may have the ability to differentiate into diverse cell types
unrelated to their phenotypical embryonic origin, including neural cells. While
demonstrated "in vitro" and neonatally, efforts to demonstrate this ability in
adult animal brains have had limited success. If it can be shown that human
MeSC (HMeSC) can differentiate into neural cells in adult brain, it would open
up the possibility that HMeSCs may be of potential therapeutic use in cell
replacement therapies for neurological diseases. Here, we demonstrate that
adult HMeSCs treated with 5-bromo-2-deoxyuridine (BrdU) for 3 weeks develop the
capability to differentiate into neural and retinal cells when provided the
appropriate lineage specific differentiation signals in vitro and in adult
animals. HMeSC without BrdU treatment did not differentiate into neurons in
vitro or adult animal or retinal cells in adult animal. Methods: MeSCs isolated from adult human bone marrow were treated
with BrdU (3 μM) for 3 weeks and then subjected to differentiation
conditions both in vitro and in vivo. Results: BrdU pretreated HMeSCs express neuronal and glial markers
after co-culture with differentiated human neural stem cells and after
transplantation into the adult rat brain. HMeSCs pretreated with BrdU and
transforming growth factor-β3 express a photoreceptor marker after
transplantation into the adult rat vitreous. Conclusions: These results suggest that BrdU treatment may increase
the multipotency of HMeSCs for possible use in autologous cell therapies for
neurological and opthamological diseases.
