Friday, April 19, 2024 4/19/2024

Evaluating the Potential of Human Induced Pluripotent Stem Cells (hiPSC) For Cartilage Repair

Award Number: R01AR070864
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Osteoarthritis is a debilitating condition associated with cartilage and joint dysfunction caused by trauma or aging that severely affects patients' quality of life resulting in a yearly burden of approximately 15 billion dollars on US healthcare. Cartilage regeneration is inherently inefficient and remains an unmet medical need that increases the propensity for development of arthritic conditions. Cell-based therapeutic approaches for repairing focal cartilage defects have utilized autologous adult chondrocytes or adult mesenchymal stem cells (MSC) but with limited success due to generation of inferior fibrocartilage and paucity of cells. An abundant autologous source like human induced pluripotent stem cells (hiPSC) is therefore attractive for engineering cartilage. Additionally, generation of developmentally `younger' chondrocytes from human iPSC akin to the neonatal or juvenile chondrocytes are expected to possess a higher regeneration potential than adult chondrocytes. The aim of this research proposal is therefore to generate iPSC and MSC from the same healthy or OA donor and comparing their potential for cartilage regeneration in vitro and in an osteochondral defect in a rat model. Towards this end, a major advance will be the generation of footprint-free human iPSC i.e. without the use of viral vectors that permanently integrate into the genome. Use of synthetic mRNA will allow generation of safe and clinically relevant hiPSC. Additionally, we have recently developed an efficient methodology to direct human iPSC (hiPSC) differentiation towards chondrocytes (or chondroprogenitor cells) using transient exposure to a series of growth factors. We will define molecular and functional characteristics of hiPSC- and hMSC-derived chondrocytes to relate with their functional capabilities. Secondly, we will optimize a biomimetic hydrogel scaffold for the maturation and implantation of human iPSC- and hMSC-derived chondrocytes. Thirdly, the potential of the human iPSC- and hMSC-derived chondrocytes to repair a focal cartilage defect will be tested in a rat model of surgically induced osteochondral defect along with long-term safety studies in mice. Collectively, these studies will help evaluate and provide a mechanistic understanding of whether a hiPSC-based cellular therapy will be superior to hMSC-based therapy and successful completion can provide the impetus to further develop a clinically applicable iPSC- based therapy for focal cartilage injury.


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 = $0 )
2024	2021	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	2/14/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $435,442 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	6/7/2021	NON-COMPETING CONTINUATION	$435,442
														Subtotal = $435,442

Issue Date FY: 2020 ( Subtotal = $449,576 )
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	6/29/2020	NON-COMPETING CONTINUATION	$449,576
														Subtotal = $449,576

Issue Date FY: 2019 ( Subtotal = $449,333 )
2019	2019	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	6/13/2019	NON-COMPETING CONTINUATION	$449,333
														Subtotal = $449,333

Issue Date FY: 2018 ( Subtotal = $448,265 )
2018	2018	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	6/21/2018	NON-COMPETING CONTINUATION	$448,265
														Subtotal = $448,265

Issue Date FY: 2017 ( Subtotal = $448,069 )
2017	2017	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	7/5/2017	NEW	$448,069
														Subtotal = $448,069

Grand Total All Awards = $2,230,685

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Evaluating the Potential of Human Induced Pluripotent Stem Cells (hiPSC) For Cartilage Repair

Award Number: R01AR070864

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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