MEGAKARYOCYTE PROGENITOR CELLS FOR PRODUCTION OF PLATELETS
First Claim
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1. An isolated population of human cells comprising at least 40% CD34+CD41+ megakaryocyte progenitor cells (MKPs), wherein said population of cells has platelet generating activity, and wherein administration of 5×
- 106 cells from the population of cells into an immunocompromised mouse results in at least 106 human platelets/ml blood 14 days post-administration.
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Abstract
Provided herein are methods of generating megakaryocyte lineage cells from hematopoietic stem cells in the absence of feeder cells and serum. The megakaryocyte progenitor cells (MKPs) generated as described result in rapid production of significant numbers of platelets when administered in vivo.
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Citations
49 Claims
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1. An isolated population of human cells comprising at least 40% CD34+CD41+ megakaryocyte progenitor cells (MKPs), wherein said population of cells has platelet generating activity, and wherein administration of 5×
- 106 cells from the population of cells into an immunocompromised mouse results in at least 106 human platelets/ml blood 14 days post-administration.
- View Dependent Claims (2, 3, 4, 6, 7, 8, 17, 18, 42)
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5. (canceled)
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9-16. -16. (canceled)
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19. A method comprising:
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culturing human CD34+ hematopoietic stem cells (HSCs) in media comprising thrombopoietin (TPO) or a TPO analog and IL-1 a under conditions that permit the CD34+ HSCs to generate a population of cells comprising CD34+CD41+ megakaryocyte progenitor cells (MKPs), wherein administration of 5×
106 cells from the population cells into an immunocompromised mouse results in at least 106 human platelets/ml blood 14 days post-administration, thereby forming a population of cells comprising MKPs. - View Dependent Claims (21, 22, 23, 24, 25)
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20. A method comprising:
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culturing human CD34+ hematopoietic stem cells (HSCs) in media comprising thrombopoietin (TPO) or a TPO analog, IL-1α
or IL-1β
, and IL-9 under conditions that permit the CD34+ HSCs to generate a population of cells comprising CD34+CD41+ megakaryocyte progenitor cells (MKPs),wherein administration of 5×
106 cells from the population cells into an immunocompromised mouse results in at least 106 human platelets/ml blood 14 days post-administration, thereby forming a population of cells comprising MKPs. - View Dependent Claims (45, 46, 47, 48)
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26-41. -41. (canceled)
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43-44. -44. (canceled)
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49-53. -53. (canceled)
Specification