Method for promoting hematopoietic and mesenchymal cell proliferation and differentiation
AssigneeUniversity of Southern California
InventorsKathleen E. Rodgers, Gere S. diZerega
Life of this patent
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Abstract
The present invention provides methods, improved cell culture medium and kits for promoting hematopoietic and mesenchymal stem and lineage-specific cell proliferation and differentiation by growth in the presence of angiotensinogen, angiotensin I (AI), AI analogues, AI fragments and analogues thereof, angiotensin II (AII), AII analogues, AII fragments or analogues thereof or AII AT2 type 2 receptor agonists, either alone or in combination with other growth factors and cytokines.
Claims60
A method of accelerating the proliferation of mesenchymal stem cells comprising contacting the mesenchymal stem cells with an amount effective to accelerate proliferation of mesenchymal stem cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R1-R8 in the sequence of general formula I
- R1—R2—R3—R4—R5—R6—R7-R8
- in which R1 and R2 together form a group of formula
- X—RA—RB—,
- wherein X is H or a one to three peptide group and a peptide bond between RA and RB is labile to aminopeptidase A cleavage;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr, excluding sequences including R4 as a terminal Tyr group.
A method of accelerating the proliferation of hematopoietic lineage-specific cells comprising contacting the hematopoietic lineage-specific cells with an amount effective to accelerate proliferation of hematopoietic lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R1-R8 in the sequence of general formula I
- R1—R2—R3—R4 —R5—R6—R7-R8
- in which R1 R2 together form a group of formula
- X—RA—RB—,
- wherein X is H or a one to three peptide group and a peptide bond between RA and RB is labile to aminopeptidase A cleavage;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), He and Tyr, excluding sequences including R4 as a terminal Tyr group.
A method of accelerating the proliferation of mesenchymal lineage-specific cells comprising contacting the mesenchymal lineage-specific cells with an amount effective to accelerate proliferation of mesenchymal lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R1-R8 in the sequence of general formula I
- R1—R2—R3—R4—R5—R6—R7-R8
- in which R1 and R2 together form a group of formula
- X—RA—RB—,
- wherein X is H or a one to three peptide group and a peptide bond between RA and RB is labile to aminopeptidase A cleavage;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr, excluding sequences including R4 as a terminal Tyr group.
A method of accelerating the proliferation of hematopoietic lineage-specific cells comprising contacting the hematopoietic lineage-specific cells with an amount effective to accelerate proliferation of hematopoietic lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous ammo acids of groups R1-R8 in the sequence of general formula I
- R1—R2—R3—R4—R5—R6—R7-R8
- in which R1 and R2 together form a group of formula
- X—RA—RB—,
- wherein X is H or a one to three peptide group and a peptide bond between RA and RB is labile to aminopeptidase A cleavage;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr, excluding sequences including R4 as a terminal Tyr group.
A method of increasing the differentiation of hematopoietic stem or lineage-specific cells comprising contacting the hematopoietic stem or lineage-specific cells with an amount effective to increase differentiation of the hematopoietic stem or lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R1-R8 in the sequence of general formula I
- R1—R2—R3—R4—R5—R6—R7-R8
- in which R1 and R2 together form a group of formula
- X—RA—RB—,
- wherein X is H or a one to three peptide group and a peptide bond between RA and RB is labile to aminopeptidase A cleavage;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr, excluding sequences including R4 as a terminal Tyr group.
An improved cell culture medium for growth of mesenchymal stem cells, wherein the improvement comprises addition to the cell culture medium of an amount effective to accelerate proliferation of mesenchymal stem cells of at least one active agent comprising a sequence, consisting of at least three contiguous amino acids of groups R1-R8 in the sequence of general formula I
- R1—R2—R3—R4—R5—R6—R7-R8
- in which R1 and R2 together form a group of formula
- X—RA—RB—,
- wherein X is H or a one to three peptide group and a peptide bond between RA and RB is labile to aminopeptidase A cleavage;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr, excluding sequences including R4 as a terminal Tyr group.
An improved cell culture medium for growth of hematopoietic lineage-specific cells, wherein the improvement comprises addition to the cell culture medium of an amount effective to accelerate proliferation of hematopoietic lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R1-R8 in the sequence of general formula I
- R1—R2—R3—R4—R5—R6—R7-R8
- in which R1 and R2 together form a group of formula
- X—RA—RB—,
- wherein X is H or a one to three peptide group and a peptide bond between RA and RB is labile to aminopeptidase A cleavage;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and. Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr, excluding sequences including R4 as a terminal Tyr group.
An improved cell culture medium for growth of mesenchymal lineage-specific cells, wherein the improvement comprises addition to the cell culture medium of an amount effective to accelerate proliferation of mesenchymal lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R1-R8 in the sequence of general formula I
- R1—R2—R3—R4—R5—R6—R7-R8
- in which R1 and R2 together form a group of formula
- X—RA—RB—,
- wherein X is H or a one to three peptide group and a peptide bond between RA and RB is labile to aminopeptidase A cleavage;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr, excluding sequences including R4 as a terminal Tyr group.
An improved cell culture medium for growth of hematopoietic lineage-specific cells, wherein the improvement comprises addition to the cell culture medium of an amount effective to accelerate proliferation of hematopoietic lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R1-R8 in the sequence of general formula I
- R1—R2—R3—R4—R5—R6—R7-R8
- in which R1 and R2 together form a group of formula
- X—RA—RB—,
- wherein X is H or a one to three peptide group and a peptide bond between RA and RB is labile to aminopeptidase A cleavage;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr, excluding sequences including R4 as a terminal Tyr group.
An improved cell culture medium for differentiation of hematopoietic stem or lineage-specific cells, wherein the improvement comprises addition to the cell culture medium an amount effective to increase differentiation of the hematopoietic stem or lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R1-R8 in the sequence of general formula I
- R1—R2—R3—R4—R5—R6—R7-R8
- in which R1 and R2 together form a group of formula
- X—RA—RB—,
- wherein X is H or a one to three peptide group and a peptide bond between RA and RB is labile to aminopeptidase A cleavage;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr,
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr, excluding sequences including R4 as a terminal Tyr group.
A kit for the propagation of mesenchymal stem cells, comprising:
- (a) an amount effective to accelerate proliferation of mesenchymal stem cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R1-R8 in the sequence of general formula I
- R1—R2—R3—R4—R5—R6—R7-R8
- in which R1 and R2 together form a group of formula
- X—RA—RB—,
- wherein X is H or a one to three peptide group and a peptide bond between RA and RB is labile to aminopeptidase A cleavage;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala, and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr, excluding sequences including R4 as a terminal Tyr group;
- and
- (b) instructions for using the amount effective of active agent as a cell culture medium supplement.
A kit for the propagation of hematopoietic lineage-specific cells, comprising:
- (a) an amount effective to accelerate proliferation of hematopoietic lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R1-R8 in the sequence of general formula I
- R1—R2—R3—R4—R5—R6—R7-R8
- in which R1 and R2 together form a group of formula
- X—RA—RB—,
- wherein X is H or a one to three peptide group and a peptide bond between RA and RB is labile to aminopeptidase A cleavage;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr, excluding sequences including R4 as a terminal Tyr group;
- and
- (b) instructions for using the amount effective of active agent as a cell culture medium supplement.
A kit for the propagation of mesenchymal lineage-specific cells, comprising:
- (a) an amount effective to accelerate proliferation of mesenchymal lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R1-R8 in the sequence of general formula I
- R1—R2—R3—R4—R5—R6—R7-R8
- in which R1 and R2 together form a group of formula
- X—RA—RB—,
- wherein X is H or a one to three peptide group and a peptide bond between RA and RB is labile to aminopeptidase A cleavage;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr,
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr, excluding sequences including R4 as a terminal Tyr group;
- and
- (b) instructions for using the amount effective of active agent as a cell culture medium supplement.
A kit for the propagation of hematopoietic lineage-specific cells, comprising:
- (a) an amount effective to accelerate proliferation of hematopoietic lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R1-R8 in the sequence of general formula I
- R1—R2—R3—R4—R5—R6—R7-R8
- in which R1 and R2 together form a group of formula
- X—RA—RB—,
- wherein X is H or a one to three peptide group and a peptide bond between RA and RB is labile to aminopeptidase A cleavage;
- f R3 is selected from the group consisting of Val, Ala, Leu, norLeu, le, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr, excluding sequences including R4 as a terminal Tyr group;
- and
- (b) instructions for using the amount effective of active agent as a cell culture medium supplement.
A kit for the differentiation of hematopoietic stem or lineage-specific cells, comprising:
- (a) an amount effective to accelerate differentiation of hematopoietic stem or lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R1-R8 in the sequence of general formula I
- R1—R2—R3—R4—R5—R6—R7-R8
- in which R1 and R2 together form a group of formula
- X—RA—RB—,
- wherein X is H or a one to three peptide group and a peptide bond between RA and RB is labile to aminopeptidase A cleavage;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr, excluding sequences including R4 as a terminal Tyr group.
- (b) instructions for using the amount effective of active agent as a cell culture medium supplement.
A method of accelerating the proliferation of mesenchymal stem cells comprising contacting the mesenchymal stem cells with an amount effective to accelerate proliferation of mesenchymal stem cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R2-R8 in the sequence of general formula II
- R2—R3—R4—R5—R6—R7—R8
- in which R2 is selected from the group consisting of H, Arg, Lys, Ala, Orn, Ser(Ac), Sar, D-Arg and D-Lys;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr.
A method of accelerating the proliferation of hematopoietic lineage-specific cells comprising contacting the hematopoietic lineage-specific cells with an amount effective to accelerate proliferation of hematopoietic lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R2-R8 in the sequence of general formula II
- R2—R3—R4—R5—R6—R7—R8
- in which R2 is selected from the group consisting of H, Arg, Lys, Ala, Orn, Ser(Ac), Sar, D-Arg and D-Lys;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr,
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), He and Tyr.
A method of accelerating the proliferation of mesenchymal lineage-specific cells comprising contacting the mesenchymal lineage-specific cells with an amount effective to accelerate proliferation of mesenchymal lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R2-R8 in the sequence of general formula II
- R2—R3—R4—R5—R6—R7—R8
- in which R2 is selected from the group consisting of H, Arg, Lys, Ala, Orn, Ser(Ac), Sar, D-Arg and D-Lys;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr.
A method of accelerating the proliferation of hematopoietic lineage-specific cells comprising contacting the hematopoietic lineage-specific cells with an amount effective to accelerate proliferation of hematopoietic lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R2-R8 in the sequence of general formula II
- R2—R3—R4—R5—R6—R7—R8
- in which R2 is selected from the group consisting of H, Arg, Lys, Ala, Orn, Ser(Ac), Sar, D-Arg and D-Lys;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr.
A method of increasing the differentiation of hematopoietic stem or lineage-specific cells comprising contacting the hematopoietic stem or lineage-specific cells with an amount effective to increase differentiation of the hematopoietic stem or lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R2-R8 in the sequence of general formula II
- R2—R3—R4—R5—R6—R7—R8
- in which R2 is selected from the group consisting of H, Arg, Lys, Ala, Orn, Ser(Ac), Sar, D-Arg and D-Lys;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Try.
An improved cell culture medium for growth of mesenchymal stem cells, wherein the improvement comprises addition to the cell culture medium of an amount effective to accelerate proliferation of mesenchymal stem cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R2-R8 in the sequence of general formula II
- R2—R3—R4—R5—R6—R7—R8
- in which R2 is selected from the group consisting of H, Arg, Lys, Ala, Orn, Ser(Ac), Sar, D-Arg and D-Lys;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr.
An improved cell culture medium for growth of hematopoietic lineage-specific cells, wherein the improvement comprises addition to the cell culture medium of an amount effective to accelerate proliferation of hematopoietic lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R2-R8 in the sequence of general formula II
- R2—R3—R4—R5—R6—R7—R8
- in which R2 is selected from the group consisting of H, Arg, Lys, Ala, Orn, Ser(Ac), Sar, D-Arg and D-Lys;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr.
An improved cell culture medium for grown of mesenchymal lineage-specific cells, wherein the improvement comprises addition to the cell culture medium of an amount effective to accelerate proliferation of mesenchymal lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R2-R8 in the sequence of general formula II
- R2—R3—R4—R5—R6—R7—R8
- in which R2 is selected from the group consisting of H, Arg, Lys, Ala, Orn, Ser(Ac), Sar, D-Arg and D-Lys;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr.
An improved cell culture medium for growth of hematopoietic lineage-specific cells, wherein the improvement comprises addition to the cell culture medium of an amount effective to accelerate proliferation of hematopoietic lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R2-R8 in the sequence of general formula II
- R2—R3—R4—R5—R6—R7—R8
- in which R2 is selected from the group consisting of H, Arg, Lys, Ala, Orn, Ser(Ac), Sar, D-Arg and D-Lys;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr,
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr.
An improved cell culture medium for differentiation of hematopoietic stem or lineage-specific cells, wherein the improvement comprises addition to the cell culture medium an amount effective to increase differentiation of the hematopoietic stem or lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R2-R8 in the sequence of general formula II
- R2—R3—R4—R5—R6—R7—R8
- in which R2 is selected from the group consisting of H, Arg, Lys, Ala, Orn, Ser(Ac), Sar, D-Arg and D-Lys;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr.
A kit for the propagation of mesenchymal stem cells, comprising:
- (a) an amount effective to accelerate proliferation of mesenchymal stem cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R2-R8 in the sequence of general formula II
- R2—R3—R4—R5—R6—R7—R8
- in which R2 is selected from the group consisting of H, Arg, Lys, Ala, Orn, Ser(Ac), Sar, D-Arg and D-Lys;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr;
- and
- (b) instructions for using the amount effective of active agent as a cell culture medium supplement.
A kit for the propagation of hematopoietic lineage-specific cells, comprising:
- (a) an amount effective to accelerate proliferation of hematopoietic lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous
- amino acids of groups R2-R8 in the sequence of general formula II
- R2—R3—R4—R5—R6—R7—R8
- in which R2 is selected from the group consisting of H, Arg, Lys, Ala, Orn, Ser(Ac), Sar, D-Arg and D-Lys;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr;
- and
- ;(b) instructions for using the amount effective of active agent as a cell culture medium supplement.
A kit for the propagation of mesenchymal lineage-specific cells, comprising:
- (a) an amount effective to accelerate proliferation of mesenchymal lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R2-R8 in the sequence of general formula II
- R2—R3—R4—R5—R6—R7—R8
- in which R2 is selected from the group consisting of H, Arg, Lys, Ala, Orn, Ser(Ac), Sar, D-Arg and D-Lys;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr, and
- (b) instructions for using the amount effective of active agent as a cell culture medium supplement.
A kit for the propagation of hematopoietic lineage-specific cells, comprising:
- (a) an amount effective to accelerate proliferation of hematopoietic lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R2-R8 in the sequence of general formula II
- R2—R3—R4—R5—R6—R7—R8
- in which R2 is selected from the group consisting of H, Arg, Lys, Ala, Orn, Ser(Ac), Sar, D-Arg and D-Lys;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr;
- and
- (b) instructions for using the amount effective of active agent as a cell culture medium supplement.
A kit for the differentiation of hematopoietic stem or lineage-specific cells, comprising:
- (a) an amount effective to accelerate differentiation of hematopoietic stem or lineage-specific cells of at least one active agent comprising a sequence consisting of at least three contiguous amino acids of groups R2-R8 in the sequence of general formula II
- R2—R3—R4—R5—R6—R7—R8
- in which R2 is selected from the group consisting of H, Arg, Lys, Ala, Orn, Se r(Ac), Sar, D-Arg and D-Lys;
- R3 is selected from the group consisting of Val, Ala, Leu, norLeu, Ile, Gly, Pro, Aib, Acpc and Tyr;
- R4 is selected from the group consisting of Tyr, Tyr(PO3)2, Thr, Ser, homoSer and azaTyr;
- R5 is selected from the group consisting of Ile, Ala, Leu, norLeu, Val and Gly;
- R6 is His, Arg or 6-NH2-Phe;
- R7 is Pro or Ala;
- and
- R8 is selected from the group consisting of Phe, Phe(Br), Ile and Tyr;
- and
- (b) instructions for using the amount effective of active agent as a cell culture medium supplement.
Dependencies are inferred from the claim text.