Ex vivo expansion of bone marrow and cord blood cells to produce stem and progenitor cells for hematopoietic reconstitution.

摘要

Ex vivo expansion of a small volume of bone marrow offers an alternate approach to cellular support for repair of a hematopoietic system damaged by radiation exposure. Unpurified bone marrow cells cultured using frequent exchange of medium (perfusion) results in (1) the growth of an adherent layer that provides a supportive microenvironment for hematopoiesis and (2) the growth of hematopoietic stem and progenitor cells. Similar increases in stem and progenitor cells were also observed in cord blood cultures using frequent medium exchange methods. An automated clinical scale system, the AastromReplicell Cell Production System, has been developed to implement the biology of this ex vivo expansion process. Clinical use of ex vivo expanded bone marrow alone or in augmenting a low dose of mobilized peripheral blood stem cells has successfully reconstituted hematopoiesis. Ex vivo expanded cord blood cells combined with unmanipulated cord blood cells have also shown significant benefits in overall survival and engraftment in pediatric and adult patients, respectively. These results suggest that ex vivo expansion of hematopoietic cells provides a mechanism for generating cells capable of hematopoietic reconstitution.