Hematopoietic Stem Cells for Perinatal Brain Injury
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,
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Hematopoietic Stem Cells for Perinatal Brain Injury Masahiro Tsuji
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. Keywords CD34-positive cell · Mononuclear cells · Umbilical cord blood cell Neonatal brain damage
M. Tsuji, M.D., Ph.D. Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan e-mail: [email protected], [email protected] © Springer Nature Singapore Pte Ltd. 2018 H. Shintaku et al. (eds.), Cell Therapy for Perinatal Brain Injury, https://doi.org/10.1007/978-981-10-1412-3_5
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M. Tsuji
5.1 Introduction Recently, hematopoietic stem cells (HSCs) have been considered a promising cell source for cell-based therapies for perinatal brain injury, in which neonatal hypoxic-ischemic encephalopathy (HIE) is the main pathophysiology. There are more than 20 reports of preclinical studies using HSCs to treat perinatal brain injuries (Table 5.1), and several clinical studies with HSCs are being conducted in patients with perinatal brain injuries (see Table 1.2 in Chap. 1). How did researchers and clinicians reach the idea that HSCs could be used for perinatal brain injuries? Two lines of thoughts likely lead to this approach. On the one hand, clinicians came to conceive that HSC transplantation (HSCT) might ameliorate brain injuries because of their successful experience with HSCT in patients with inborn errors of metabolism or neurodegenerative disorders. On the other hand, neuroscientists in the field of cell therapies came to think that HSCs might be a feasible alternative for cell-based therapy for brain injuries because other candidate
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