Multipotent adult progenitor cells improve the hematopoietic function in myelodysplasia

Autor: Satish Khurana, Thomas Vanwelden, Dorien Broekaert, Esther Wolfs, Valerie D. Roobrouck, Catherine M. Verfaillie, Kathleen Sels, Michel Delforge, Nancy Boeckx, Larissa Lhoest, Shubham Pandey, Soumen Chakraborty, Christophe Deroose, Peter Vandenberghe, Chloé Hoornaert, Bryan Holvoet, Tom Struys, Peter Ponsaerts
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Cytotherapy
ISSN: 1465-3249
Popis: Background aims Myelodysplastic syndromes (MDS) are a group of clonal stem cell disorders affecting the normal hematopoietic differentiation process and leading to abnormal maturation and differentiation of all blood cell lineages. Treatment options are limited, and there is an unmet medical need for effective therapies for patients with severe cytopenias. Methods We demonstrate that multipotent adult progenitor cells (MAPC) improve the function of hematopoietic progenitors derived from human MDS bone marrow (BM) by significantly increasing the frequency of primitive progenitors as well as the number of myeloid colonies. Results This effect was more pronounced in a non-contact culture, indicating the importance of soluble factors produced by the MAPC cells. Moreover, the cells did not stimulate the growth of the abnormal MDS clone, as shown by fluorescent in situ hybridization analysis on BM cells from patients with a known genetic abnormality. We also demonstrate that MAPC cells can provide stromal support for patient-derived hematopoietic cells. When MAPC cells were intravenously injected into a mouse model of MDS, they migrated to the site of injury and increased the hematopoietic function in diseased mice. Discussion The preclinical studies undertaken here indicate an initial proof of concept for the use of MAPC cell therapy in patients with MDS-related severe and symptomatic cytopenias and should pave the way for further investigation in clinical trials.
Databáze: OpenAIRE
Externí odkaz: