Abstract
Studies have shown that adult bone marrow derived stem cells (MSCs) can participate in repair of myocardial injury in adult hearts, as well as in cardiac growth during fetal development in utero. Yet, no studies have evaluated the role of MSCs with respect to normal growth or tissue repair in immature hearts after birth. The present study examines whether MSCs may participate in the myocardial growth and injury in the post-natal immature hearts. MSCs were isolated from adult Lewis rats and labeled with Lac-Z gene using retroviral vectors. These MSCs were injected systemically into groups of neonatal (NB=2days-old), immature (B=30days-old) and adult (A=>3months-old) isogeneic Lewis rats. Additionally, left coronary artery ligation was carried out in subgroups of immature (BL) and adult (AL) rats one week after MSCs injection. The hearts were harvested serially from 2-days to 6-weeks, stained with X-Gal for labeled MSCs. Cardiomyocyte phenotypic expression was evaluated by immunohistological staining for Troponin I-C and Connexin-43. Labeled MSCs were found to home into the bone marrow in all rats of different developmental stages. They could be recruited from bone marrow into the infarcted site of myocardium only in groups AL and BL. They were also capable of differentiating into cardiomyocyte phenotype after myocardial injury. In contrast to that reported in the developing fetus, MSCs did not appear to contribute to the growth of non-injured hearts after birth. However, they can be recruited from the bone marrow and regenerate damaged myocardium both in the adult and in the immature hearts.
Highlights
There is considerable evidence indicating that bone marrow stromal cells (MSCs) contain multipotent stem cells that can be induced to differentiate into cells of various phenotypes including cardiomyocytes, both in vitro [1] and in vivo [2]
Experimental and early clinical studies reveal that these cells can survive and engraft into the peri-infracted myocardium where they can differentiate to participate in the repair process [3]
Our study suggests that MSCs administrated systemically have no significant toxicity to the normal growing individuals, are capable of homing to the bone marrow following intravenous [9] or intraperitoneal infusion
Summary
There is considerable evidence indicating that bone marrow stromal cells (MSCs) contain multipotent stem cells that can be induced to differentiate into cells of various phenotypes including cardiomyocytes, both in vitro [1] and in vivo [2]. Experimental and early clinical studies reveal that these cells can survive and engraft into the peri-infracted myocardium where they can differentiate to participate in the repair process [3]. These studies had been done so far exclusively in mature animals and adult humans with no data on pediatric age group. The donor MSCs could be detected for up to 5 months in various fetal tissues, suggesting that the implanted MSCs could participate in growth and organogenesis during fetal development.
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