Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

The Use of Senolytic and Anti-Fibrotic Agents to Improve the Beneficial Effect of Bone Marrow Stem Cells for Osteoarthritis

Award Number: UH3AR077748
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2020
PERIOD OF PERFORMANCE END DATE: 07/31/2025

Group Awards By:

View Award Description

The Use of Senolytic and Anti-Fibrotic Agents to Improve the Beneficial Effect of Bone Marrow Stem Cells for Osteoarthritis - Abstract: Osteoarthritis (OA) is a progressive joint disease leading to cartilage damage, pain and loss of function. While many stem cell therapies for OA are under investigation, none are currently FDA-approved for modifying the course of the disease. Of the many adult stem cell types potentially applicable to OA, bone marrow stem cells (BMSCs) from bone marrow aspirate concentrate (BMC) are the most clinically translatable (and are already in clinical use) since they can be harvested using minimally invasive technology and do not require in vitro expansion. There is, however, significant potential for improving efficacy of BMSC treatment for OA. The number of senescent cells in BMC increases with age and OA, and these cells release pro-inflammatory cytokines/chemokines, proteases, and other senescence-associated secretory phenotypes (SASP) that can impair stem cell function and likely contribute to OA development/progression. Dr. Kirkland’s laboratory (co- investigator) has identified compounds that specifically kill senescent cells, abrogating systemic SASP factors. We have shown that these senolytic agents can delay OA in a preclinical model. We have also shown that blocking fibrosis with Losartan (a TGF-β1blocker) can improve cartilage repair by promoting regeneration of hyaline cartilage while reducing the amount of fibrocartilage. Thus, we hypothesize that administration of senolytic and/or anti-fibrotic agents will enhance the beneficial effect of BMSCs for treating OA. We propose to perform, a randomized clinical trial at The Steadman Clinic (TSC) and Steadman Philippon Research Institute (SPRI). This phase I/II trial will evaluate the safety and efficacy of Fisetin (a senolytic dietary supplement) and Losartan (an anti-fibrotic drug), used either individually or in combination, for improving the clinical efficacy of BMSCs in the treatment of knee osteoarthritis. The senolytic (Fisetin 1000mg/day, previously FDA IND approved) regimen will be cycles of 2 days on/28 days off, administered before and 3 months after BMSC treatment. The anti-fibrotic (Losartan, 25mg/day, previously IND-exempted) will be administered for 30 days starting immediately after BMSC treatment. OA knee joints will undergo MRI at baseline and 18 months post- treatment to assess changes in cartilage morphology and structure over time. Patient-reported outcomes for pain and function will be collected at baseline and 3, 6, 12 & 18 months. Joint and cartilage function will be assessed using video-motion analysis at baseline and 18 months. OA biomarkers related to cartilage degeneration, inflammation and pain will be assessed at baseline and 18 months. Blood and synovial fluid will be evaluated at baseline, 4 days and 18 months after treatment to assess changes in cellular senescence and OA biomarkers. This trial will build upon a currently active clinical trial on orthobiologics for OA treatment at SPRI (utilizing the same patient population and outcomes assessments), demonstrating the ability of our teams to perform the proposed study and also leveraging the combined trials to effectively provide a 6-arm, comprehensive assessment of biological therapies for improving treatment of OA.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $551,586 )
2024	2024	STEADMAN PHILIPPON RESEARCH INSTITUTE	181 W MEADOW DR STE 1000	VAIL	CO	81657	EAGLE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	8/5/2024	NON-COMPETING CONTINUATION	$551,586
														Subtotal = $551,586

Issue Date FY: 2023 ( Subtotal = $600,051 )
2023	2023	STEADMAN PHILIPPON RESEARCH INSTITUTE	181 W MEADOW DR STE 1000	VAIL	CO	81657	EAGLE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	8/24/2023	NON-COMPETING CONTINUATION	$600,051
														Subtotal = $600,051

Issue Date FY: 2022 ( Subtotal = $621,091 )
2022	2022	STEADMAN PHILIPPON RESEARCH INSTITUTE	181 WEST MEADOW DRIVE	VAIL	CO	81657	EAGLE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	8/22/2022	NON-COMPETING CONTINUATION	$621,091
														Subtotal = $621,091

Issue Date FY: 2021 ( Subtotal = $790,325 )
2021	2021	STEADMAN PHILIPPON RESEARCH INSTITUTE	181 WEST MEADOW DRIVE	VAIL	CO	81657	EAGLE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	8/11/2021	EXTENSION WITH OR WITHOUT FUNDS	$633,825
2021	2021	STEADMAN PHILIPPON RESEARCH INSTITUTE	181 WEST MEADOW DRIVE	VAIL	CO	81657	EAGLE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	8/12/2021	SUPPLEMENT FOR EXPANSION	$156,500
														Subtotal = $790,325

Grand Total All Awards = $2,563,053

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The Use of Senolytic and Anti-Fibrotic Agents to Improve the Beneficial Effect of Bone Marrow Stem Cells for Osteoarthritis

Award Number: UH3AR077748

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/01/2020

PERIOD OF PERFORMANCE END DATE: 07/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer