Perivascular stem cell composition for bone

• US 9,730,965 B2
• Filed: 02/10/2012
• Issued: 08/15/2017
• Est. Priority Date: 08/20/2009
• Status: Expired due to Fees

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Peault, Bruno, Soo, B. Chia, Ting, Kang
• Primary Examiner(s): JOHNSON, KARA D
• Application Number:
  US13/371,330
• Publication Number:
  US 20120244128A1
• Time in Patent Office: 2,013 Days
• Field of Search: 424 937, 424484
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/44 Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

Embodiments of the present invention provide an osteogenic composition comprising perivascular stem cells or induced pluripotent cells (iPS) and an osteogenic agent and methods of making and using the same.

Claims

1. A composition for bone regeneration, comprising:

an isolated population of perivascular stem cells (PSC), and

an osteoinductive agent,

wherein the osteoinductive agent is in a therapeutically effective amount for causing the isolated population of PSC to differentiate in the osteoblast lineage or in a therapeutically effective amount for enhancing the survivability or engraftment of the isolated population of PSC where the PSC provide trophic factors or enhance vascular ingrowth, and

wherein the PSC are selected from the group consisting of adventitial cells showing positive expression of CD34;

adventitial cells showing positive expression of CD34 and negative expression of CD146, NG2, PDGF-β

, CD45 and CD31;

adventitial cells showing positive expression of CD34 and negative expression of CD146, CD45 and CD31;

adventitial cells showing positive expression of CD34 and negative expression of CD146 and CD31; and

a combination thereof.

2. The composition of claim 1, wherein the osteoinductive agent is a NELL-1 factor.

3. The composition of claim 1, wherein the PSC has a density of about 1×

10⁴ to about 1×

10⁸ per 1 mL volume of the composition.

4. The composition of claim 1, which is effective for osteoporosis.

5. The composition of claim 1, which is an osteogenic implant.

6. The composition of claim 1, which is an implant for spine fusion.

7. The composition of claim 1, further comprises an excipient.

8. The composition of claim 1, wherein the osteoinductive agent is a NELL-1 factor, and wherein the composition is an osteogenic scaffold.

9. The composition of claim 1, wherein the PSC further comprise pericytes showing positive expression of CD146, NG2, and PDGF-β

and negative expression of CD45, CD34 and CD56;

pericytes showing positive expression of CD146, NG2, and PDGF-β and

negative expression of CD45, CD34 and CD31;

or pericytes showing positive expression of CD146 and negative expression of CD45, CD34 and CD31.

10. A method of treating or ameliorating a bone condition, comprising:

administering to a subject a composition according to claim 1.

11. The method of claim 10, wherein the bone condition is a spine condition or osteoporosis.

12. A method of fabricating a composition for bone regeneration, comprising:

providing an osteoinductive agent,

providing an isolated population of perivascular stem cells (PSC), and

forming the composition,

wherein the osteoinductive agent is in a therapeutically effective amount for causing the isolated population of PSC to differentiate in the osteoblast lineage or in a therapeutically effective amount for enhancing the survivability or engraftment of the isolated population of PSC where the PSC provide trophic factors or enhance vascular ingrowth, and

wherein the PSC are selected from the group consisting of adventitial cells showing positive expression of CD34;

adventitial cells showing positive expression of CD34 and negative expression of CD146, NG2, PDGF-β

, CD45 and CD31;

adventitial cells showing positive expression of CD34 and negative expression of CD146, CD45 and CD31;

adventitial cells showing positive expression of CD34 and negative expression of CD146 and CD31; and

a combination thereof.

13. The method of claim 12, wherein the osteoinductive agent is a NELL-1 factor.

14. The method of claim 12, wherein the PSC has a density of about 1×

10⁴ to about 1×

10⁸ per 1 mL volume of the composition.

15. The method of claim 12, wherein the composition is effective for osteoporosis.

16. The method of claim 12, wherein the composition is an osteogenic implant.

17. The method of claim 12, wherein the composition is an implant for spine fusion.

18. The method of claim 12, wherein the composition further comprises an excipient.

19. The method of claim 12, wherein the osteoinductive agent is a NELL-1 factor, and wherein the composition is an osteogenic scaffold.

20. The method of claim 12, wherein the PSC further comprise pericytes showing positive expression of CD146, NG2, and PDGF-β

and negative expression of CD45, CD34 and CD56;

pericytes showing positive expression of CD146, NG2, and PDGF-β and

negative expression of CD45, CD34 and CD31;

or pericytes showing positive expression of CD146 and negative expression of CD45, CD34 and CD31.