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

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $449,576

## Abstract

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.

## Key facts

- **NIH application ID:** 9953983
- **Project number:** 5R01AR070864-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Nidhi Bhutani
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $449,576
- **Award type:** 5
- **Project period:** 2017-07-05 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9953983

## Citation

> US National Institutes of Health, RePORTER application 9953983, Evaluating the Potential of Human Induced Pluripotent Stem Cells (hiPSC) For Cartilage Repair (5R01AR070864-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9953983. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*