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How to increase hematopoietic stem cell engraftment and transplant outcome?


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.

approach
examples
references
phase
Increase yield of HSC by isolation procedure
1. cord + placental blood HSC

2. improving CB processing

1. HemaCell Perfusion system [1]



2. BioE PrepaCyte-CB [2]

preclinical – phase I
HSC expansion ex vivo
using cytokine cocktails or “artificial niche” bioreactors StemEx Gamida Cell [3] phase II-III
co-transplantation with cells increasing engraftment
1. myeoid progenitors

2. mesenchymal cells

1. Cellerant CLT-08 [4]

2. Pluristem PLX-I [5]

1. phase I



2. preclinical – phase I

co-transplantation with few HSC sources
1. double (multiple) unit CB

2. CB + MB of BM from 3rd party donors

1. NCT00514579 [6]



2. Bone Marrow Transplant 2009; 43: 365 [7]

1. phase II-III



2. phase I

new conditioning regiments
making more niches available in host BM Science 2007; 5854: 1296 [8] preclinical
new routes to transplantation of HSC intra-bone bone marrow transplant Lancet Oncology 2008;9:831 [9] phase I-II

CB – cord blood; BM – bone marrow; MB – mobilized blood



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