Hematopoietic stem cells for perinatal brain injury

Abstract

Hematopoietic stem cells (HSCs) and cell fractions containing HSCs derived from bone marrow or umbilical cord blood have emerged as promising tools for cell-based therapies for perinatal brain injury. Nearly 20 studies in models of perinatal brain injury, most of which are rodent models of neonatal hypoxia-ischemia, have histologically and functionally demonstrated beneficial effects of systemic administration of HSCs and the related cell fraction. Studies have shown that the cell therapies are beneficial even if the cells are administered up to days after the insult. The cells do not directly differentiate into neurons or glial cells, nor do they regenerate damaged brain tissue. Instead, they elicit beneficial effects via other mechanisms, such as by modulating inflammatory/immune responses and increasing the levels of trophic factors, separate from their hematopoietic properties. Cell therapy with HSCs or the cell fraction containing HSCs has several advantages over other types of cell therapies. This approach does not require intracranial transplantation; intravenous transfusion seems sufficient for them to exert their beneficial effects. The cells are easily obtained, and neither gene manipulation nor cell culture is required. These advantages make HSC therapy feasible for translation into clinical use for infants with brain injury. The optimal protocol, however, has yet to be determined in further preclinical studies.