The most significant limitation of using of hematopoietic stem cell transplantation for treatment hematological and non-hematological diseases is a low number of progenitor/stem cells in the graft. For sufficient engraftment and good clinical outcome 2-5 millions of CD34+ cells should be transplanted. Unfortunately, many cell products, especially cord blood samples contain less number of stem cells than required.
Here I was trying to summarize some approaches used for improvement of engraftment by mostly increasing stem cell number per graft. The top part of the table represents approaches which have a potential to be commercialized.
|Increase yield of HSC by isolation procedure
||1. cord + placental blood HSC
2. improving CB processing
|1. HemaCell Perfusion system||preclinical – phase I|
|HSC expansion ex vivo
||using cytokine cocktails or “artificial niche” bioreactors||StemEx Gamida Cell||phase II-III|
|co-transplantation with cells increasing engraftment
||1. myeoid progenitors
2. mesenchymal cells
|1. Cellerant CLT-08||
1. phase I
|co-transplantation with few HSC sources
||1. double (multiple) unit CB
2. CB + MB of BM from 3rd party donors
|1. NCT00514579||1. phase II-III
|new conditioning regiments
||making more niches available in host BM||Science 2007; 5854: 1296||preclinical|
|new routes to transplantation of HSC||intra-bone bone marrow transplant||Lancet Oncology 2008;9:831||phase I-II|
CB – cord blood; BM – bone marrow; MB – mobilized blood
Let me know if I missed something.