Methods of using JNK or MKK inhibitors to modulate cell differentiation and to treat myeloproliferative disorders and myelodysplastic syndromes
First Claim
1. A method of modulating the differentiation of a mammalian stem cell comprising contacting the stem cell with a compound that modulates JNK or MKK activity, under conditions suitable for differentiation of said stem cell.
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Abstract
The present invention provides methods of modulating mammalian, particularly human, stem cell and progenitor cell differentiation to regulate and control the differentiation and maturation of these cells along specific cell and tissue lineages. The methods of the invention relate to the use of certain small organic molecules to modulate the differentiation of stem cell populations along specific cell and tissue lineages, particularly embryonic-like stem cells originating from a postpartum placenta or stem cells isolated form sources such as cord blood. The invention also relates to the treatment or prevention of myelodysplastic syndrome or myeloproliferative syndrome, or symptoms thereof, comprising administration of JNK or MKK inhibitors, alone or in combination, as well as with or without the use of unconditioned cells or cells conditioned in accordance with other aspects of the invention. Finally, the invention relates to the use of such differentiated stem cells in transplantation and other medical treatments.
288 Citations
58 Claims
- 1. A method of modulating the differentiation of a mammalian stem cell comprising contacting the stem cell with a compound that modulates JNK or MKK activity, under conditions suitable for differentiation of said stem cell.
- 3. A method of conditioning a mammalian stem cell comprising contacting the stem cell with a compound that modulates JNK or MKK activity.
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6. A method of transplanting a mammalian stem cell or progenitor cell to a patient in need thereof comprising:
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(a) contacting the stem cell or progenitor cell with a compound that inhibits JNK activity to produce a treated stem cell or progenitor cell; and
(b) transplanting the treated stem cell into said patient. - View Dependent Claims (7, 8, 9)
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- 10. A method of producing a hematopoietic cell comprising contacting a mammalian stem cell with a compound that inhibits JNK or MKK activity under conditions suitable for differentiation of the stem cell, wherein said differentiation results in the production of a hematopoictic cell.
- 18. A pharmaceutical composition comprising a mammalian stem cell and a pharmaceutically-acceptable carrier, wherein said stem cell has been contacted with a compound that inhibits JNK or MKK activity for a time sufficient to cause modulation of differentiation or proliferation of said stem cell.
- 19. A pharmaceutical composition comprising a mammalian progenitor cell and a pharmaceutically-acceptable carrier, wherein said stem cell has been contacted with a compound that inhibits JNK or MKK activity for a time sufficient to cause modulation of differentiation or proliferation of said progenitor cell.
- 31. A pharmaceutical composition comprising in a pharmaceutically acceptable carrier isolated cord blood cells and an isolated population of white blood cells, wherein the white blood cells are generated by a method comprising differentiating a stem cell under suitable conditions and in the presence of a compound that inhibits JNK activity or MKK activity, and isolating the white blood cells differentiated thereby.
- 32. A pharmaceutical composition comprising isolated cord blood cells and an isolated population of white blood cells, wherein the white blood cells are generated by a method comprising differentiating a stem cell under suitable conditions and in the presence of a compound that inhibits JNK activity or MKK activity, and isolating the white blood cells differentiated thereby.
- 38. A method of treating a mammalian subject in need of white blood cells comprising differentiating a stem cell or a progenitor cell under suitable conditions and in the presence of a compound that inhibits JNK or MKK activity, wherein said differentiating produces white blood cells, and administering a therapeutically effective amount of said white blood cells to said mammalian subject.
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47. A method of transplanting bone marrow in a patient in need thereof, comprising transplanting to said patient cord blood, stem cells obtained from cord blood, peripheral blood or stem cells obtained from peripheral blood, wherein said cord blood, stem cells obtained from cord blood, peripheral blood or stem cells have been contacted with an inhibitor of JNK or MKK activity for a time sufficient to cause modulation of differentiation or proliferation of said stem cells.
- 51. A method of treating or preventing a myeloproliferative disorder, comprising administering to a patient in need thereof an effective amount of a JNK inhibitor or an MKK inhibitor.
- 53. A method for treating or preventing a symptom of or an abnormality associated with a myeloproliferative disorder, comprising administering to a patient in need thereof an effective amount of a JNK inhibitor or an MKK inhibitor.
- 55. A method for treating or preventing a myelodysplastic syndrome, comprising administering to a patient in need thereof an effective amount of a JNK inhibitor or an MKK inhibitor.
- 57. A method for treating or preventing a symptom of a myelodysplastic syndrome, comprising administering to a patient in need thereof an effective amount of a JNK inhibitor or an MKK inhibitor.
Specification