Injections with secretome from trabecular meshwork stem cells to treat glaucoma-related symptoms.
Glaucoma is the leading cause of irreversible blindness worldwide. An estimated 64 million people are affected each year, a number projected to rise to 111 million by 2040 as the global population ages. In glaucoma, increased intraocular pressure (IOP) in the eye damages the optic nerve that connects the eye to the brain, resulting in vision loss. The University of Pittsburgh has patented stem cell-based therapies to regenerate the trabecular meshwork (TM) that allows fluid to drain, reducing IOP. Stem cell-free therapies using stem cell secretome is an attractive treatment strategy for glaucoma with low risk and little invasiveness, especially for populations with religious limitations or high sensitivity.
Technology Description
The secretome derived from trabecular meshwork stem cells (TMSCs) has been found to reduce IOP in two glaucoma mouse models of steroid-induced and inherited glaucoma. Treatment with secretome by periocular injection leads to dramatic IOP reduction to a normal range for up to two months, as well as improved retina function similar to normal animals. Secretome reduced fibrosis in wounded TM cells, increased TM cells’ wound healing capacity, and protected retinal ganglion cell from death. The safety evaluation did not indicate any side effects with secretome treatment.Advantages
Periocular injection is effective and minimal invasive
Can be applied as eye drops or eye ointments
No side effects
Production is efficient, scalable, and reproducible
Can be stored for years without losing therapeutic efficacyApplications
As eye drops or eye ointments or periocular injection for glaucoma treatment and preventing vision lossStage of Development
In vitro and in vivo data; xenograft experiments have been completed with very promising resultsIP Status
Provisional patent application filedRelated Technology
[2257] Trabecular Meshwork Stem Cells
InnovatorsYiqin Du, MD, PhD
Associate Professor Ophthalmology & Developmental Biology, University of Pittsburgh School of Medicine
Dr. Du’s research focuses on stem cell biology and glaucoma; in particular, her lab focuses on trabecular meshwork regeneration to prevent glaucomatous vision loss, retinal ganglion cell regeneration, and corneal regeneration using different stem cell types and their trophic factors including secretome and exosomes.Education
PhD, Ophthalmology, Beijing University, Beijing, China
MD, Clinical Medicine, Xuzhou Medical University, Jiangsu, ChinaSelect Publications
Yiqin Du, Eric Carlson, Martha L. Funderburgh, Naxin Guo, David E. Birk, Winston W. Kao, James L. Funderburgh. Stem Cell Therapy Restores Transparency to Defective Murine Corneas. Stem Cells. 2009, 27 (7): 1635-1642. PMID: 19544455.
Hongmin Yun, Yiwen Wang, Yi Zhou, Ke Wang, Ming Sun, Donna B. Stolz, Xiaobo Xia, C. Ross Ethier, Yiqin Du. Human stem cells home to and repair laser-damaged trabecular meshwork in a mouse model. Communications Biology, (2018) 1:216 | DOI: 10.1038/s42003-018-0227-z. eCollection 2018. PMID: 30534608.
Yiwen Wang, Deborah Osakue, Enzhi Yang, Yi Zhou, Haiyan Gong, Xiaobo Xia, Yiqin Du. ER Stress Response of Trabecular Meshwork Stem Cells and TM Cells and Protective Effects of Activated PERK Pathway. Invest. Ophthalmol. Vis. Sci. 2019, 60(1): 265-73. PMID: 30654386.
Xiong S, Xu Y, Wang Y, Kumar A, Peters DM, Du Y. α5β1 Integrin Promotes Anchoring and Integration of Transplanted Stem Cells to the Trabecular Meshwork in the Eye for Regeneration. Stem Cells Dev. 2020 Mar 1;29(5):290-300. PubMed PMID: 31854234; PubMed Central PMCID: PMC7047116.
Zhou Y, Xia X, Yang E, Wang Y, Marra KG, Ethier CR, Schuman JS, Du Y. Adipose-derived stem cells integrate into trabecular meshwork with glaucoma treatment potential. FASEB J. 2020 May;34(5):7160-7177. PubMed PMID: 32259357; PubMed Central PMCID: PMC7254553.
Xiong S, Kumar A, Tian S, Taher E, Yang E, Kinchington P, Xia X, Du Y. Stem cell transplantation rescued a primary open-angle glaucoma mouse model. eLife. 2021 January 28; 10:e63677. PubMed Central PMCID: PMC7864631.Ajay Kumar, PhD
Postdoctoral Research Associate, University of Pittsburgh School of Medicine
Dr. Kumar’s research focuses on stem cell biology and glaucoma; RGC regeneration, 3D retina organoids and harnessing the power of stem cell paracrine factors broadly defined as secretome.Education
PhD, Stem Cell Biology, PGIMER, Chandigarh, IndiaSelect Publications
Kumar, Ajay, et al. “Secretome Proteins Regulate Comparative Osteogenic and Adipogenic Potential in Bone Marrow and Dental Stem Cells.” Biochimie, vol. 155, 2018, pp. 129–139., doi:10.1016/j.biochi.2018.10.014.
Kumar, Ajay, et al.. “Molecular spectrum of secretome regulates the relative hepatogenic potential of mesenchymal stem cells from bone marrow and dental tissue”. Scientific Reports, (2017) 7:15015
Kumar A, Xu Y, Du Y. Stem Cells from Human Trabecular Meshwork Hold the Potential to Develop into Ocular and Non-Ocular Lineages After Long-Term Storage. Stem Cells Dev. 2020 Jan 1;29(1):49-61. PubMed PMID: 31680626.
Kumar A, Xiong S, Du Y, et al. Stem cell-free therapy for glaucoma to preserve vision. Submitted.