X-Message-Number: 24239
Date: Sun, 13 Jun 2004 13:37:55 -0700 (PDT)
From: Doug Skrecky <>
Subject: Are you as young as your bone marrow?

Circ Res. 2002 May 31;90(10):E89-93.
Young adult bone marrow-derived endothelial precursor cells restore
aging-impaired cardiac angiogenic function.
  Delivery of young bone marrow-derived stem cells offers a novel approach
for restoring the impaired senescent cardiac angiogenic function that may
underlie the increased morbidity and mortality associated with ischemic
heart disease in older individuals. Recently, we reported that
alterations in endothelial cells of the aging heart lead to a
dysregulation in the cardiac myocyte platelet-derived growth factor
(PDGF)-B-induced paracrine pathway, which contributes to impaired cardiac
angiogenic function. Based on these results, we hypothesized that
cellular restoration of the PDGF pathway by bone marrow-derived
endothelial precursor cells (EPCs) could reverse the aging-associated
decline in angiogenic activity. In vitro studies revealed that young
murine (3-month-old) bone marrow-derived EPCs recapitulated the cardiac
myocyte-induced expression of PDGF-B, whereas EPCs from the bone
marrow of aging mice (18-month-old) did not express PDGF-B when cultured
in the presence of cardiac myocytes. Transplantation of young, but not
old, genetically marked syngeneic bone marrow cells into intact,
unirradiated aging mice that populated the endogenous senescent murine
bone marrow incorporated into the neovasculature of subsequently
transplanted syngeneic neonatal myocardium. Moreover, the young bone
marrow-derived EPCs restored the senescent host angiogenic PDGF-B
induction pathway and cardiac angiogenesis, with graft survival and
myocardial activity in the aging murine host (cardiac allograft viability:
3-month-old controls, 8/8; 18-month-old controls, 1/8; 18-month-old
donors receiving bone marrow from 3-month-old mice, 15/16; or
18-month-old mice, 0/6; P<0.05). These results may offer a foundation for
the development of novel therapies for the prevention and
treatment of cardiovascular disease associated with aging.

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