# Enhancing the potency of aged adult stem cells for tissue reconstruction

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $339,900

## Abstract

ABSTRACT
More than half a million patients undergo surgeries to repair of large bony defects every year.
However, the two primary options currently available for bone reconstruction are the use of bone
harvested from the patient suffering from the injury by additional surgeries, or bone grafts from
cadaver donors. However, these multiple operations incur significant morbidity on the patient. Thus,
bone engineering offers an attractive alternative approach for regenerative medicine. Mesenchymal
stem cells (MSCs) have a great potential for engineering bone grafts and have been shown to
generate bone cells in-vitro in three dimensional (3D) scaffolds. However, the therapeutic application
of human MSCs in bone regeneration and reconstruction is still limited by a physiological aging
related decline in their differentiation potential, compromising the feasibility and reproducibility of
therapies. Moreover, bone grafts generated from MSCs are only millimeters in size limiting their use
in a clinical setting. Telomere shortening restricts cell proliferation and ultimately leads to in-vitro
aging and loss of function. We have designed a highly innovative approach, to overcome these
challenges based on preliminary data from our laboratory showing that the differentiation potency of
aged MSCs can be restored by the factor ZSCAN4. Our overall goal is to design novel protocols
generate bone grafts suitable for the treatment of degenerative bone diseases and bone
reconstructive surgeries. In this application we will a. Establish a clinically scaled bone graft from
tonsil derived human MSCs. b. Define the effects of ZSCAN4 on bone differentiation potential of aged
and in vitro aged MSCs as a mean to allow the scalability to human bone size requirements. c.
Determine the role of ZSCAN4 in regulation of stemness potency.

## Key facts

- **NIH application ID:** 9988161
- **Project number:** 5R01AR070819-04
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Michal Zalzman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $339,900
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988161

## Citation

> US National Institutes of Health, RePORTER application 9988161, Enhancing the potency of aged adult stem cells for tissue reconstruction (5R01AR070819-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9988161. Licensed CC0.

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