Kathy E. Mitchell

Potential Treatment of Cerebral Global Ischemia with Oct-4+ Umbilical Cord Matrix Cells

Potential therapeutic effects of Oct‐4‐positive rat umbilical cord matrix (RUCM) cells in treating cerebral global ischemia were evaluated using a reproducible model of cardiac arrest (CA) and resuscitation in rats. Animals were randomly assigned to four groups: A, sham‐operated; B, 8‐minute CA without pretreatment; C, 8‐minute CA pretreated with defined media; and D, 8‐minute CA pretreated with Oct‐4+ RUCM cells. Pretreatment was done 3 days before CA by 2.5‐μl microinjection of defined media or approximately 104 Oct‐4+ RUCM cells in left thalamic nucleus, hippocampus, corpus callosum, and cortex. Damage was assessed histologically 7 days after CA and was quantified by the percentage of injured neurons in hippocampal CA1 regions. Little damage (approximately 3%–4%) was found in the sham group, whereas 50%–68% CA1 pyramidal neurons were injured in groups B and C. Pretreatment with Oct‐4+ RUCM cells significantly (p < .001) reduced neuronal loss to 25%–32%. Although the transplanted cells were found to have survived in the brain with significant migration, few were found directly in CA1. Therefore, transdifferentiation and fusion with host cells cannot be the predominant mechanisms for the observed protection. The Oct‐4+ RUCM cells might repair nonfocal tissue damage by an extracellular signaling mechanism. Treating cerebral global ischemia with umbilical cord matrix cells seems promising and worthy of further investigation.

Umbilical Cord Stem Cells

The two most basic properties of stem cells are the capacities to self-renew and to differentiate into multiple cell or tissue types (1, 2, 3). Generally, stem cells are categorized as one of three types: embryonic stem cells (ES), embryonic germ cells (EG), or adult stem cells. ES cells are derived from the inner cell mass of the blastula (Fig. 1). They proliferate indefinitely and can differentiate spontaneously into all three tissue layers of the embryo (4) and into germ cells as well (5, 6, 7). EG cells are derived from primordial germ cells (see (Fig. 1), a small set of stem cells that reside in the protected environment of the yolk stalk, so that they remain undifferentiated during embryogenesis. As with ES cells, EG cells have the capacity to differentiate into all three tissue layers (8). Adult stem cells are found in most tissues and in the circulation. They may have less replicative capacity than ES or EG cells and, until recently, were thought to have restricted developmental fates (9). This classification system omits a significant source of stem cells derived from the extraembryonic tissues (umbilical cord, placenta and amniotic tissues/fluids), which are derived from neither the adult organism nor the embryo proper. This review will describe studies of stem cells derived from extraembryonic tissues with an emphasis on cells derived from umbilical cord, their developmental origins, and relationships to other types of stem cells and potential in regenerative medicine.