Umbilical Cord Blood Cells Engraft and Differentiate in Cardiac Tissues after Human Transplantation.

Kirsten B. Crapnell, Kristi Turner, Jennifer Hall, Susan Staba, Joanne Kurtzberg Pediatric Bone Marrow Transplantation, Duke University Medical Center, Durham, NC, USA

Introduction: Umbilical cord blood (UCB) stem cells can successfully rescue the blood and immune system after myeloblative transplantation. Preclinical studies have shown that hematopoietic cells from bone marrow and umbilical cord blood have the ability to transdifferentiate into tissue other then those specified by their origin. We asked whether hematopoietic stem cells from UCB have the ability to differentiate into cardiac muscle in transplanted patients with pre-existing cardiac pathology. Methods: An unfortunate child with Sanfilippo Syndrome Type B (Mucopolysaccharide (MPS) III) transplanted with a sex mismatched unrelated UCB unit at 4 years of age, engrafted but died 5 months post-transplant of respiratory failure due to an adenoviral infection. With parental consent, his heart was studied in order to determine whether donor derived cells had engrafted and/or differentiated at the time of his death. At autopsy heart tissue was fixed in formalin, embedded in paraffin, and stored for future evaluation. Approximately 2 months later, cardiac tissue was cut into 5 micron thick sections, dehydrated, and stained with antibodies (Troponin I-C and myosin heavy chain) against cardiac specific antigens. These same heart sections were then counterstained with FISH for XY chromosomes to differentiate donor and host cells. Results: We found extensive distribution of female donor cells in blood vessels throughout the heart (63% of total cells enumerated). Rarer donor cells were also found through the myocardium in cells with patterns exhibiting the cross-striations of striated muscle. Donor cells stained positive for Troponin I-C (specific for cardiac muscle Troponin I) and for myosin heavy chain (1-2 cells per 10-20 high power fields). Conclusion: We documented engraftment and differentiation of donor UCB cells into cardiac myocytes in a child transplanted for MPS III. It is possible that donor cells may selectively homed to damaged myocardium and subsequently differentiated in situ. After engraftment, differentiation into myocardial cells may improve cardiac function and subsequently diminish the likelihood of progressive heart failure with its attendant morbidity and mortality in patients with MPS syndromes.

Abstract #4324 appears in Blood, Volume 102, issue 11, November 16, 2003