Proliferation and Differentiation of Progenitor Cells Throughout the Intact Adult Rat Spinal Cord

Abstract

The existence of multipotent progenitor populations in the adult forebrain has been widely studied. To extend this knowledge to the adult spinal cord we have examined the proliferation, distribution, and phenotypic fate of dividing cells in the adult rat spinal cord. Bromodeoxyuridine (BrdU) was used to label dividing cells in 13- to 14-week-old, intact Fischer rats. Single daily injections of BrdU were administered over a 12 d period. Animals were killed either 1 d or 4 weeks after the last injection of BrdU. We observed frequent cell division throughout the adult rodent spinal cord, particularly in white matter tracts (5-7% of all nuclei). The majority of BrdU-labeled cells colocalized with markers of immature glial cells. At 4 weeks, 10% of dividing cells expressed mature astrocyte and oligodendroglial markers. These data predict that 0.75% of all astrocytes and 0.82% of all oligodendrocytes are derived from a dividing population over a 4 week period. To determine the migratory nature of dividing cells, a single BrdU injection was given to animals that were killed 1 hr after the injection. In these tissues, the distribution and incidence of BrdU labeling matched those of the 4 week post injection (pi) groups, suggesting that proliferating cells divide in situ rather than migrate from the ependymal zone. These data suggest a higher level of cellular plasticity for the intact spinal cord than has previously been observed and that glial progenitors exist in the outer circumference of the spinal cord that can give rise to both astrocytes and oligodendrocytes.

Cell Therapy for Multiple Sclerosis

“…Multi-potential precursors are abundant in many regions of the adult brain parenchyma [31][32][33][34]. In particular, oligodendrocyte progenitor cells (OPCs) were isolated from various regions of the adult rodent CNS [35][36][37], and were identified also in the adult human brain [38][39][40][41][42] and spinal cord [43]. OPCs are identified by expression of chondroitin-sulfate proteoglycan NG2+ and of platelet-derived growth factor receptor-α are highly abundant in the adult CNS, comprising up to 5% of its cells [37].…”

Do glial cells control pain?

“…Fortunately, antibodies are available to recognize BrdU by immunohistochemistry. Microglia are rarely dividing in the intact spinal cord (Horner et al, 2000). However, microglia proliferation occurs after nerve injury (Graeber et al, 1988) and was found in diverse models of neuropathic pain.…”

Adult Spinal Cord Stem/Progenitor Cells Transplanted as Neurospheres Preferentially Differentiate into Oligodendrocytes in the Adult Rat Spinal Cord

“…Stem/progenitor cells have been iden- (4,14,17,25,29,30,42,44) or intrathecal administration of mitogenic growth factors (16,19). In lower vertebrates, tified in the adult rat and mouse spinal cord (14,15,17,24,(28)(29)(30)36,46,47). In response to injury, these cells ependymal cells rapidly proliferate, migrate, and differentiate to regenerate the adult spinal cord (9,31,37).…”