Bromodeoxyuridine increases multipotency of human bone marrow-derived stem cells

Restor Neurol Neurosci. 2004;22(6):459-68.

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 muM) 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-beta3 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / physiology
  • Brain / metabolism
  • Bromodeoxyuridine / pharmacology*
  • Cell Differentiation / drug effects*
  • Cell Size / drug effects
  • Cells, Cultured
  • Coculture Techniques / methods
  • Dose-Response Relationship, Drug
  • Glial Fibrillary Acidic Protein / metabolism
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Immunohistochemistry / methods
  • In Situ Hybridization / methods
  • Indoles
  • Male
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / physiology
  • Neurons / physiology*
  • Oligonucleotide Array Sequence Analysis / methods
  • RNA, Messenger / metabolism
  • Rats
  • Retina / drug effects
  • Retina / physiology
  • Rod Opsins / genetics
  • Rod Opsins / metabolism
  • Stem Cell Transplantation / methods
  • Stem Cells / physiology
  • Time Factors
  • Tubulin / metabolism

Substances

  • Antiviral Agents
  • Glial Fibrillary Acidic Protein
  • Indoles
  • RNA, Messenger
  • Rod Opsins
  • TUBB3 protein, human
  • Tubb3 protein, rat
  • Tubulin
  • Green Fluorescent Proteins
  • DAPI
  • Bromodeoxyuridine