Stem—Like Cells, Human Brain

THERE ARE DIFFERENT kinds of stem cells (e.g., embryonic, adult, and cancer stem cells), and studying the nature and behaviors of different stem cell populations simultaneously provides insights into the roles for these very potent cells during normal and abnormal tissue generation. Stem cells are known for their innate ability to give rise to more developed daughter cells while at the same time maintaining a population of themselves. The asymmetric cellular divisions that give rise to different kinds of progenitor cells from stem cells, along with the unique environments in which they live, their so—called niches, are being studied in a variety of models with the goal of using these special cells and factors that control their growth and differentiation for tissue and organ repair.

Embryonic stem cells can give rise to all tissues and organs, and we now know that adult tissues and organs possess populations of so—called adult or somatic stem cells; even the adult human brain has an adult stem cell population that resides in a region around the fluid—filled spaces, or ventricles, and that has the potential to be mobilized for brain and spinal cord repair. Recent studies have focused on the use of novel cell culture or in vitro protocols to simulate the generation of brain cells as it occurs in the living brain during normal development, aging, and brain tumor generation. In vitro systems have replicated brain cell generation, or neurogenesis, from the postnatal [Page 532]and adult brain stem cells we call multipotent astrocytic stem cells (MASCs), isolated from biopsy and even postmortem human brain tissue specimens. MASCs are glial in origin; there are two major classes of cells in the nervous system, neuronal and glial cells, with the latter generally appreciated as being support cells for the message—sending neurons. Many research groups have now shown that a cell with many, if not all, of the attributes of a glial cell, referred to as an astrocyte, can behave as a stemlike cell in the adult human brain and can give rise to both neurons and glia (hence its multipotency). These MASCs hold great promise for being tapped as neuronal progenitors that can provide new neurons that are lost to injury or disease, including degenerative diseases such as Parkinson's disease and Alzheimer's disease, where neurons are lost, contributing to behavioral déficits. New ways to encourage these adult stem—like cells in the human brain and spinal cord to protect or replace at—risk neuron populations in human neurological diseases are the intense focus of many researchers who study cellular transplantation and drug discovery to encourage the innate reparative potential of these cells.

There is another class of glial cell in the adult human brain that exhibits neural progenitor cell behaviors, adult human neural progenitor cells, or AHNPs, which have been isolated and expanded from the adult human cerebral cortex—a structure not normally known to retain stem or progenitor cells throughout life. A great deal of attention has been focused on embryonic and fetal cells, but there is relatively little known about the plasticity of such adult somatic cells. Using techniques similar to those developed for isolating, expanding, and characterizing embryonic stem cells and MASCs, novel cell culture conditions have revealed an unprecedented proliferative capacity of AHNPs such that a single proliferating AHNP, which again exhibits adult astrocyte qualities, can produce replacement cells for almost 50 million adult human brains. These AHNPs are targets for drug—screening and pharmacological manipulation in the injured or diseased central nervous system with the potential for autologous, or self—repair, therapeutic approaches for neurological disease. It appears that both AHNPs and MASCs might respond to molecular cues present in the injured or diseased brain with regenerative attempts, but there is now a pressing need to discover drugs and factors that facilitate this inherent reparative ability of glial stem—like cells in our brains for life.

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