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Rare Incorporation of Bone Marrow-Derived Cells Into Kidney After Folic Acid-Induced Injury

^a Research Division, Nephros Therapeutics Inc., Ann Arbor, Michigan;
^b University of Michigan Comprehensive Cancer Center and
^c Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA

Key Words. Bone marrow transplant • Transdifferentiation • Kidney • Bone marrow-derived Folic acid • Adult stem cells • Acute renal failure

Correspondence: Mark S. Szczypka, 1995 Highland Drive, Suite F, Ann Arbor, MI 48108, USA. Telephone: 734–975–0080; Fax: 734–975–0090; e–mail: mszczypka{at}nephrostherapeutics.com

Results obtained in recent experiments suggest that bone marrow-derived cells (BMDCs) engraft into tissues and differentiate into various somatic cell types. However, it is unclear whether injury is required for the phenomenon to occur at appreciable frequencies. In this study we tested whether BMDCs engraft into kidneys and differentiate into renal cells in the absence or presence of toxic injury. Renal damage was induced by delivery of folic acid (FA) to bone marrow (BM)-recipient mice 1 or 9 months after bone marrow transplant, and kidneys were examined for donor-derived cells 2,4, or 8 weeks after injury. Donor-derived cells were abundant in the renal interstitium of injured kidneys and were detected in glomeruli of vehicle- and FA-treated mice. Most of these cells expressed the common leukocyte antigen CD45 and display morphological characteristics of white blood cells. No donor-derived renal tubule cells (RTCs) were detected in kidney sections of BM-recipient mice. However, in cell culture, a cluster of seven donor-derived cells of 4 x 10⁶ RTCs examined (~ 0.0002%) displayed morphological characteristics of RTCs. CD45+ cells of donor origin were also detected in glomeruli and glomerular outgrowths. Nested polymerase chain reaction analysis for the male-specific Sry gene in cultured RTCs and glomerular outgrowths confirmed the presence of donor-derived cells. These results suggest that BMDCs may incorporate into glomeruli as specialized glomerular mesangial cells; however, BMDCs rarely contribute to the repair of renal tubules in uninjured or FA-treated mouse kidneys.

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