# Mesenchymal Stem Cells can Restore and Maintain Corneal Endothelial Function

> **NIH NIH K99** · SCHEPENS EYE RESEARCH INSTITUTE · 2022 · $106,339

## Abstract

Project Summary
In this project, we propose to investigate the ability of mesenchymal stem cell (MSCs) to differentiate into
functionally active corneal endothelial cells (CECs) to be transplanted in the diseased eye. As sources of MSCs,
bone marrow MSCs (BM-MSCs), limbus MSCs (L-MSCs), and adipose derived MSCs (A-MSCs) will be
evaluated. We will (1) determine the differentiation potential of different MSCs by varying numerous parameters
and evaluate different molecular pathways involved in their differentiation, and (2) determine the ability of the
differentiated cells to regenerate functionally active endothelium in diseased conditions. The differentiation,
characterization, biocompatibility, and functionalization studies proposed here through in vitro, ex vivo, and in
vivo studies will offer qualitative and quantitative information of the degree of biointegration and regenerative
potential of the differentiated cells in contact with the host´s corneal cells and extracellular matrix. We expect
that CECs differentiated from MSCs can proliferate in vivo after transplantation, maintaining the optimal hydration
of the corneal stroma. If autologous or allogeneic MSCs can be differentiated to CECs and transplanted to
recover normal endothelial function in patients suffering from endothelial diseases, without causing any immune
or inflammatory response and without using whole donor corneas (DCs), this could simplify the treatment of
corneal endothelial diseases and increase availability of DCs for other types of keratoplasty. Thus, I believe, this
proposed research plan has the potential to revolutionize the treatment of corneal diseases, not only those
affecting the corneal endothelium but also those affecting other corneal layers. The research aims are supported
by the training plan focused on the acquisition of relevant multidisciplinary expertise in the field of cell and
molecular biology, physiopathology, tissue-engineering, gene therapy, and material science. To this end, a
“Mentoring Team” which includes the lead mentor, Dr. James Chodosh (MEE/ SERI), along with co-mentors, Dr.
Miguel Gonzalez (SERI/UOC) and Professor Shigeto Shimmura (Keidai), has been assembled. Moreover, three
independent collaborators will support our team in (1) the design of the studies related to MSCs differentiation
and characterization (Dr. Garzon), (2) understanding of molecular pathways involved in the differentiation (Dr.
Sabater), and (3) the nanoparticle based MRI detectable therapeutic strategies design (Dr. Patra). This group of
mentors and collaborators will guide me during the K99 phase to achieve my long term career goal of becoming
an academic scientist, and leader in my field with a strong independent research background. I envision that this
award will provide me with an excellent platform to transition to an independent research faculty member (this
includes the transition into the R00 phase) and in the long term, to successfully compete for independent N...

## Key facts

- **NIH application ID:** 10465019
- **Project number:** 5K99EY031373-02
- **Recipient organization:** SCHEPENS EYE RESEARCH INSTITUTE
- **Principal Investigator:** Mohammad Mirazul Islam
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $106,339
- **Award type:** 5
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465019

## Citation

> US National Institutes of Health, RePORTER application 10465019, Mesenchymal Stem Cells can Restore and Maintain Corneal Endothelial Function (5K99EY031373-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10465019. Licensed CC0.

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