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: BackgroundBone marrow–derived stem cells are involved in tissue formation in transplanted organs. In human renal cell transplants, recipient-specific cells have been shown to participate in regeneration of interstitial tissue. In hepatic transplants, hepatocytes with a recipient sex chromosome pattern have been observed. Recruitment of stem cells in repair and regeneration of cardiac myocytes has been demonstrated in experimental ischemia. Recently, cardiac antral myocytes of recipient origin have been shown to populate transplanted hearts in gender-mismatched transplants.: MethodsUsing the flourescence in situ hybridization (FISH) technique we examined serial post-transplant right ventricular biopsies and sections of ventricle (at time of autopsy) of 4 gender-mismatched female-to-male transplanted hearts (graft survival 0.5 to 10 years, mean 5.1 years) for Y chromosomes within cardiac myocytes.: ResultsWe detected recipient-specific sex chromosomal patterns in single rare cardiac myocytes in 1 case in a serial biopsy after 7 years of transplant survival. The other serial biopsies, as well as the final sections at autopsy, showed no recipient pattern chromosomes within the myocytes. In addition, 2 cases demonstrated Y chromosomes in the smooth muscle of intracardiac arteries.: ConclusionDevelopment of recipient marrow–derived stem cells into functional myocytes in the ventricle of transplanted hearts is a rare feature. The higher percentage of stem cell population in the cardiac atria may be a feature of tissue repair and/or an early feature of transplant physiology. Similar to other transplant organs, recipient stem cells are involved in tissue neovascularization. [Copyright &y& Elsevier]

Pulmonary alveolar proteinosis (PAP) due to deficiency of the common β-chain (βc) of the interleukin–3 (IL–3)/IL–5/granulocyte–macrophage colony–stimulating factor (GM–CSF) receptors is a rare monogeneic disease characterized by functional insufficiency of pulmonary macrophages. Hematopoietic stem cell gene therapy for restoring expression of βc-protein in the hematopoietic system may offer a curative approach. Toward this end, we generated a retroviral construct expressing the murine βc (mβc) gene and conducted investigations in a murine model of βc-deficient PAP. Functional correction of mβc activity in mβc–/– bone marrow (BM) cells was demonstrated by restoration of in vitro colony formation in response to GM-CSF. In addition, in a murine in vivo model of mβc-deficient PAP mβc gene transfer to hematopoietic stem cells not only restored the GM-CSF-sensitivity of hematopoietic progenitor cells but also, within a period of 12 weeks, almost completely reversed the morphologic features of surfactant accumulation. These results were obtained despite modest transduction levels (10–20%) and, in comparison to wild-type mice, clearly reduced βc expression levels were detected in hematopoietic cells. Therefore, our data demonstrating genetic and functional correction of mβc–/– deficiency in vitro as well as in a murine in vivo model of PAP strongly suggest gene therapy as a potential new treatment modality in βc-deficient PAP.Molecular Therapy (2008); 16 4 757–764 doi:10.1038/mt.2008.7 [ABSTRACT FROM AUTHOR]