IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2010;2(1):20-28.

Short Communication
Diabetes and aging alter bone marrow contributions to tissue maintenance

Chunlin Wang, Ronald A. Seifert, Daniel F. Bowen-Pope, Kevin C. Kregel, Martine Dunnwald, Gina C. Schatteman

Department of Integrative Physiology, FH 424, University of Iowa, Iowa City, IA 52242, USA; Department of Pathology, Box 358050,
University of Washington, Seattle, WA 98195, USA; 3Department of Pediatrics, 206 MRC, University of Iowa, Iowa City, IA 52242, USA.

Received October 29, 2009; accepted November 15, 2009; available online November 23, 2009

Abstract: Bone marrow-derived cells contribute to repair of injured tissue and to the maintenance of tissue homeostasis, but the extent
to which perturbations of systemic homeostasis modulate this contribution is unknown. Accordingly, hematopoietic chimeras were
used to determine contributions of bone marrow-derived cells to hepatocytes, skeletal muscle myocytes, and cardiomyocytes in healthy
young, healthy old, and young obese diabetic mice. Mice with multiple genomic copies of a non-expressed β-globin/pBR322 sequence
served as bone marrow donors. Because detection of the integrated sequence does not involve gene expression and many copies of
the sequence are present, the sensitivity of detection is high and is not influenced by the state of cell differentiation. Our data indicate
that bone marrow contributes a significant fraction of hepatocytes in old and diabetic mice, but half as many in young mice. They also
show that bone marrow is a significant source of new cardiomyocytes at all ages and that this contribution is unaffected by diabetes.
Additionally we found that bone marrow makes a substantial contribution to skeletal myocyte replacement that decreases with age. In
summary, bone marrow-derived cells contribute significantly to normal non-hematopoietic cell replacement, a contribution that is
altered by overall homeostatic state in a tissue specific manner. These data are significant if we are to understand if, and if so how,
bone marrow-derived cell dysfunction contributes to tissue damage and senescence. (IJPPP910003).

Key words: Adult bone marrow stem cells, diabetes mellitus, aging, homeostasis, bone marrow cells, mice

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Address all correspondence to:
Martine Dunnwald, Pharm. D, PhD,
500 Newton Road, 206
MRC, Iowa City, IA, 52242, USA.
Tel: 319-384-4645; FAX: 319-335-6970