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Blood, 15 August 2005, Vol. 106, No. 4, pp. 1479-1487.
Prepublished online as a Blood First Edition Paper on April 12, 2005; DOI 10.1182/blood-2004-11-4282.
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Submitted November 12, 2004
Accepted April 3, 2005
Effects of aging on the homing and engraftment of murine hematopoietic stem and progenitor cells
Ying Liang, Gary Van Zant*, and Stephen J Szilvassy
Departments of Physiology and Internal Medicine, University of Kentucky, Lexington, KY, USA
* Corresponding author; email: gvzant1{at}uky.edu.
To test the hypothesis that aging has negative effects on stem cell homing and engraftment, young or old C57BL/6 BM cells were injected, using a limiting-dilution, competitive transplant method, into old or young Ly5 congenic mice. Numbers of hematopoietic stem cells (HPCs) and progenitor cells (HPCs) recovered from BM or spleen were measured and compared to the numbers initially transplanted. Although the frequency of marrow competitive repopulation units (CRU) increased ~2-fold from 2 months to 2 years of age, the BM homing efficiency of old CRU was ~3-fold lower than that of young CRU. Surprisingly, the overall size of individual stem cell clones generated in recipients transplanted with a single CRU was not affected by donor age. However, increased age of both HSC donors and transplant recipients caused a marked skewing of the pattern of engraftment toward the myeloid lineage, indicating that both HSC-intrinsic and HSC-extrinsic (microenvironmental) age-related changes favor myelopoiesis. This correlated with changes post-transplant in the rate of recovery of circulating leukocytes, erythrocytes, and platelets. Recovery of the latter was especially blunted in aged recipients. Collectively, these findings may have implications for clinical HSC transplantation where older individuals increasingly serve as donors for elderly patients.
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