Transforming growth factor beta (TGF-β) blocking agent-treated stem cell composition and method
First Claim
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1. A method of decreasing the time for hematopoietic reconstitution of a patient following chemotherapy or radiation therapy, comprising:
- (a) obtaining a population of cells containing human stem cells from a subject;
(b) enriching for the human stem cells in said population;
(c) exposing the enriched stem cell population, ex vivo, to an oligomer antisense to TGF-β
, under culture conditions and for a period of time effective to block the effect of TGF-β
on replication and/or differentiation of said stem cells;
(d) culturing the antisense oligomer treated stem cells to obtain cultured TGF-β
blocking agent-treated stem cells, wherein the viability and differentiation state of said stem cells is maintained for at least 5 days; and
(e) administering said cultured TGF-β
blocking agent-treated stem cells to a subject, wherein the time required for in vivo reconstitution of at least one hematopoietic lineage is reduced relative to that of a subject who received stem cells not treated with an oligomer antisense to TGF-β
.
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Abstract
The invention relates to TGF-β blocking agent-treated HSC compositions and methods comprising the same. The TGF-β blocking agent-treated stem cells are viable for an extended time in culture without replication or differentiation and upon transfer to appropriate conditions are capable of long term hematopoietic reconstitution.
138 Citations
6 Claims
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1. A method of decreasing the time for hematopoietic reconstitution of a patient following chemotherapy or radiation therapy, comprising:
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(a) obtaining a population of cells containing human stem cells from a subject;
(b) enriching for the human stem cells in said population;
(c) exposing the enriched stem cell population, ex vivo, to an oligomer antisense to TGF-β
, under culture conditions and for a period of time effective to block the effect of TGF-β
on replication and/or differentiation of said stem cells;
(d) culturing the antisense oligomer treated stem cells to obtain cultured TGF-β
blocking agent-treated stem cells, wherein the viability and differentiation state of said stem cells is maintained for at least 5 days; and
(e) administering said cultured TGF-β
blocking agent-treated stem cells to a subject, wherein the time required for in vivo reconstitution of at least one hematopoietic lineage is reduced relative to that of a subject who received stem cells not treated with an oligomer antisense to TGF-β
. - View Dependent Claims (2, 3, 4, 5, 6)
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Specification