Utilizing Age-Specific Adipocyte Progenitor Cells for Cell Therapy in Older Patients
Grant Award Details
Grant Type:
Grant Number:
DISC0-15689
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$1,508,997
Status:
Active
Grant Application Details
Application Title:
Utilizing Age-Specific Adipocyte Progenitor Cells for Cell Therapy in Older Patients
Public Abstract:
Research Objective
A new type of APC serves older patients as 1) better MSC in immunomodulation (reducing inflammation) for autologous transplantation; 2) better source of somatic cells for generating heathier hiPSCs.
Impact
Bottlenecks: 1) Older patients suffer from sarcopenic obesity, which has no safe and effective treatment. 2) Cell therapy in older patients is often not satisfactory due to stem cell aging.
Major Proposed Activities
A new type of APC serves older patients as 1) better MSC in immunomodulation (reducing inflammation) for autologous transplantation; 2) better source of somatic cells for generating heathier hiPSCs.
Impact
Bottlenecks: 1) Older patients suffer from sarcopenic obesity, which has no safe and effective treatment. 2) Cell therapy in older patients is often not satisfactory due to stem cell aging.
Major Proposed Activities
- Determination of the adipogenic capacity of human CP-As. Characterization of the ability of human CP-As to differentiate into other cell types, including osteoblasts, chondrocytes, and muscle cells.
- Determine the function of LIFR in human CP-As through LIFR agonist/antagonist treatments, virus-mediated gene manipulations, in a 3D culture system in vitro, and in a transplantation assay in vivo.
- Inducible eliminate new adipocytes generated during aging in a new mice model and determine the metabolic benefits. Comparison of the function of human adipocytes generated from CP-As vs. young APCs.
- Establish a high-throughput screening platform that is efficient, effective, and consistent for inhibiting human CP-A differentiation to prevent age-related fat expansion and select top hits.
- Evaluate the immunomodulating capacity of human CP-As, compared to classic bone marrow MSCs, in secreting anti-inflammatory cytokines and inhibiting immune cell proliferation.
- Evaluate the advantages of iPSCs derived from CP-As, compared to iPSCs derived from the blood cells of the same human donor, in DNA damage rate, iPSC marker expression, and differentiation efficiency.
Statement of Benefit to California:
California has the largest number of older residents. Many older residents of underserved communities reside in so-called "food deserts”, leading to sarcopenic obesity and many chronic disorders. We will explore the potential for using a newly identified adult fat stem cell to prevent and treat sarcopenic obesity, or be used for immunomodulation cell therapies, or serve as a source of somatic cell for generating better human induced pluripotent stem cells (hiPSCs) for autologous transplantation.