Successful Allogeneic Stem Cell Transplant in Pediatric Patients With Diminished Left Ventricular Ejection Fractions.

Chemotherapy-associated cardiotoxicity may delay or impair the ability to administer fully myeloablative chemotherapy for stem cell transplant in those with reduced left ventricular ejection fraction. Studies in adults have been inconsistent regarding the value of ejection fraction in predicting cardiotoxicity in the posttransplant period. Recent publications, however, have demonstrated successful stem cell transplantation in adults despite low ejection fractions. This case series highlights 2 pediatric patients who were successfully treated with stem cell transplantation without posttransplant cardiac complications, despite pretransplant ejection fractions of 38% and 29%.

Megakaryocytes Enhance Mesenchymal Stromal Cells Proliferation and Inhibit Differentiation.

Megakaryocytes (MKs) can induce proliferation of calvarial osteoblasts [Ciovacco et al., 2009], but this same phenomenon has not been reported for bone marrow stromal populations from long bones. Bone marrow contains several types of progenitor cells which can be induced to differentiate into multiple cell types. Herein, we examined mesenchymal stromal cell proliferation and osteoblastic differentiation when rabbit or mouse MK were cultured with i) rabbit bone marrow stromal cells, ii) rabbit dental pulp stromal cells, or iii) mouse bone marrow stromal cells. Our results demonstrated that rabbit and mouse stromal cells co-cultured with rabbit MK or mouse MK, have significant increases in proliferation on day 7 by 52%, 46%, and 24%, respectively, compared to cultures without MK. Conversely, alkaline phosphatase (ALP) activity was lower at various time points in these cells when cultures contain MK. Similarly, calcium deposition observed at day 14 rabbit bone marrow and dental pulp stromal cells and day 21 mouse bone marrow stromal cells was 63%, 69%, and 30% lower respectively, when co-cultured with MK. Gene expression studies reveal transcriptional changes broadly consistent with increased proliferation and decreased differentiation. Transcript levels of c-fos (associated with cell proliferation) trended higher after 3, 7, and 14 days in culture. Also, expression of alkaline phosphatase, osteonectin, osterix, and osteopontin, which are markers for osteoblast differentiation, showed MK-induced decreases in a cell type and time dependent manner. Taken together, these data suggest that MK play a role in stromal cell proliferation and differentiation, from multiple sites/locations in multiple species. This article is protected by copyright. All rights reserved.