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Cardiac Compositions

a technology of compositions and pscs, applied in the field of compositions of cardiac vessels, can solve the problems of limited availability and inability to adapt to small-diameter (id6mm) vascular applications of current synthetic grafts, and achieve the effect of enhancing vascular ingrowth and survivability or engrafting of ps

Inactive Publication Date: 2012-09-20
RGT UNIV OF CALIFORNIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a composition that includes a population of perivascular stem cells (PSC) or induced pluripotent stem cells (iPS) and a cardioinductive agent. The cardioinductive agent can be a chemical or biological agent that causes the stem cells to differentiate in the cardiac cell or progenitor lineages so as to generate cardio tissues. The composition can also enhance the survivability or engraftment of the stem cells. The stem cells can be autologous or allogeneic, and can be embedded in a scaffold or a vascular graft. The composition can be formulated into different formulations and can be used to treat, delay, or ameliorate cardiac or cardiovascular conditions. The method of fabricating the composition involves providing a population of PSC or iPS and a cardioinductive agent. The implantable device includes a composition of PSC or iPS and a cardioinductive agent. The technical effects of the invention include providing a therapeutically effective amount of a cardioinductive agent to regenerate cardio tissues and enhance the survivability or engraftment of stem cells.

Problems solved by technology

Although autologous grafts are the gold standard for bypass procedures, they are limited by availability.
Current synthetic grafts are not suitable for small-diameter (ID<6mm) vascular applications due to the acute thrombosis [3-5].
However, MSCs have shortcomings, e.g., heterogenicity and limited availability.

Method used

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  • Cardiac Compositions
  • Cardiac Compositions

Examples

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example 1

Isolation of Adventitia PSC from Liposuction Aspirate

[0147]SVF Isolation from Liposuction Aspirate.

[0148]Liposuction aspirate was washed with an equal volume of PBS and centrifuged for 10 minutes at 400×g. After centrifugation, the top layer of the preparation, representing the tissue fraction containing the SVF, was collected and further washed in PBS. The tissue fraction was then enzymatically processed by addition of an equal volume of digestion solution (DMEM, collagenase II 1 mg / ml, DNAse 10 μg / ml, 1% Pen-Strepto, 3% BSA) and incubation for 45 minutes at 37 C under agitation (250 rpm). The enzymatic digestion was stopped after addition of PBS 5mM EDTA and the solution was filtered through 100 μm cell strainer. After two washes in PBS 5mM EDTA and centrifugation at 400×g for 10 minutes, the supernatant containing adipocytes was discarded and the pellet was resuspended in 10 ml red blood cell lysis buffer for 10 minutes at room temperature. The suspension was washed in PBS 5mM ED...

example 2

Cardiogenic Studies on Pericytes and NELL-1

[0151]Studies on cardiogenic ability of pericytes and NELL-1 factor were performed in a SCID mouse thigh muscle implantation model. The results are shown in FIGS. 1 and 2. FIG. 1 shows increased pericyte proliferation / survival when Nell-1 is added. FIG. 2 shows increased VEGF expression by pericytes when Nell-1 is added.

[0152]The above results clearly documented the cardiogenic ability of pericytes and NELL-1. These experiments demonstrate the effects of NELL-1 for enhancing survivability and engraftment of PSC or iPS and for causing PSC or iPS to differentiate into cardiac cell or progenitor cell lineage so as to generate a cardio tissue.

[0153]While particular embodiments of the present invention have been shown and described, it are obvious to those skilled in the art that changes and modifications can be made without departing from this invention in its broader aspects. Therefore, the appended claims are to encompass within their scope a...

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Abstract

Embodiments of the present invention provide a composition comprising perivascular stem cells or induced pluripotent cells (iPS) and a NELL-1 factor for cardiac or vascular regeneration and methods of making and using the same.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of PCT / US2010 / 002298, filed on Aug. 20, 2010, which claims the benefit of U.S. provisional application No. 61 / 235,618, filed on Aug. 10, 2009. The teaching in these applications is incorporated hereto in its entirety by reference.TECHNICAL FIELD OF THE INVENTION[0002]The present invention generally relates to cardiac compositions comprising perivascular stem cells or induced pluripotent stem cells and NELL-1 protein and methods of making and using the same.BACKGROUND OF THE INVENTION[0003]Cardiovascular disease accounts for 1 in every 2.8 deaths in the United States and costs approximately $475 billion in 2009 [1]. 56% of these deaths come from diseases of peripheral and coronary arteries, the latter resulting in 500,000 coronary artery bypass grafts (CABG) each year [1]. Together with CABG, lower limb revascularization and arteriovenous access grafts for hemodialysis account for more than 1 million vasc...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K35/12A61L27/54A61P9/00A61L27/38A61K9/00A61P9/10A61K35/44
CPCA61K35/44A61K38/1709A61K2300/00A61P9/00A61P9/10A61P19/00A61P19/08A61P19/10
Inventor SOO, B. CHIATING, KANGPEAULT, BRUNO
Owner RGT UNIV OF CALIFORNIA
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