The natural course of aging, as well as the progression of several degenerative diseases, closely correlates with a loss of adult stem cell quantity and function. Adult stem cells exist in nearly all tissue types in the body and are responsible for maintaining normal tissue turnover and regenerating damaged or injured tissues. Stem cells maintain and repair tissues by reproducing, differentiating into other cell types, and releasing growth and signaling factors to regulate the behavior of nearby cells. Injecting muscle-derived stem cells harvested from young mice can recover the loss of stem cell proliferation and function observed in older mice, and in addition to anti-aging applications, mice with simulated Hutchinson-Gilford progeria syndrome significantly extended lifespan and improved health after stem cell injection. This indicates the therapeutic potential of stem cells from younger donors or stem cells banked early in a patient’s life to ameliorate the symptoms of degenerative diseases or aging.
Technology Description
This technology is a therapeutic method of administering autologous or allogenic stem cells isolated from younger donors in order to restore or rejuvenate adult stem cell function. This technology offers therapeutic potential by administering isolated allogenic healthy adult stem cells and an mTOR inhibitor and releasing secreted growth and signaling factors from those stem cells into a degenerative or injured tissue. After administration, these therapies rejuvenate these damaged tissues in otherwise healthy mammals and delay or reverse signs of aging-related symptoms such as progeria.Advantages
Stem cell transplants eliminate the need for pharmacologic therapies
Delays progression of degenerative progeria-type syndromesApplications
Anti-aging
Treating the symptoms of degenerative diseases, like Hutchinson-Gilford progeria syndrome.Stage of Development
In vivo dataIP Status
Niedernhofer LJ, Lavasani M, Robbins PD, Huard J. Compositions and Methods for Restoring or Rejuvenating Stem/Progenitor Cell Function. US 9,295,696. United States Patent and Trademark Office. Patent granted on 29 March 2016.
Niedernhofer LJ, Lavasani M, Robbins PD, Huard J. Compositions and Methods for Restoring or Rejuvenating Stem/Progenitor Cell Function. US 10,293,001. United States Patent and Trademark Office. Patent granted on 21 May 2019.Relevant publications
Niedernhofer, L., Huard, J., et al. Muscle-derived stem/progenitor cell dysfunction limits healthspan and lifespan in a murine progeria model. Nature Communications. 2012. 3(608). DOI: 10.1038/ncomms1611Innovators
Johnny Huard, PhD
Former faculty member
Henry J. Mankin Professor and Vice Chair, Musculoskeletal Cellular Therapeutics
Director, Stem Cell Research Center, Department of Orthopaedic Surgery
Deputy Director, Cellular Therapeutics Research, McGowan Institute for Regenerative Medicine
Dr. Huard, who spent over twenty years as an endowed professor at the University of Pittsburgh, was honored for his work at Pitt with the Kappa Delta Ann Doner Vaughan Award commemorating lifetime achievement. His research focuses on gene therapy, tissue engineering, regenerative medicine, and aging applications based on the use of muscle-derived stem cells, especially with regards to their translation to a clinical setting.Education
Postdoctoral, Gene Therapy, University of Pittsburgh
Postdoctoral, Gene Therapy, McGill University
PhD, Neurobiology, Laval University
Laura J. Niedernhofer, MD, PhD
Former adjunct professor, Department of Microbiology & Molecular Genetics
Dr. Niedernhofer’s research interests include aging and age-related diseases, DNA damage, transgenic mouse models, rare genome instability disorders, and senescence. Her career has been dedicated to investigating the impact of DNA damage on the structure of DNA, cell function, and organism health.Education
PhD, Biochemistry, Vanderbilt University School of Medicine
MD, Vanderbilt University School of MedicineSelect Joint Publications
Kawakami Y, Hambright WS, Takayama K, Mu X, Lu A, Cummins JH, Matsumoto T, Yurube T, Kuroda R, Kurosaka M, Fu FH, Robbins PD, Niedernhofer LJ, Huard J. Rapamycin Rescues Age-Related Changes in Muscle-Derived Stem/Progenitor Cells from Progeroid Mice. Mol Ther Methods Clin Dev. 2019 May 30;14:64-76. doi: 10.1016/j.omtm.2019.05.011. eCollection 2019 Sep 13.
Hambright WS, Niedernhofer LJ, Huard J, Robbins PD. Murine models of accelerated aging and musculoskeletal disease. Bone. 2019 Aug;125:122-127. doi: 10.1016/j.bone.2019.03.002. Epub 2019 Mar 4.
Zhao J, Zhang L, Mu X, Doebelin C, Nguyen W, Wallace C, Reay DP, McGowan SJ, Corbo L, Clemens PR, Wilson GM, Watkins SC, Solt LA, Cameron MD, Huard J, Niedernhofer LJ, Kamenecka TM, Robbins PD. Development of novel NEMO-binding domain mimetics for inhibiting IKK/NF-κB activation. PLoS Biol. 2018 Jun 11;16(6):e2004663. doi: 10.1371/journal.pbio.2004663. eCollection 2018 Jun.
Proto JD, Lu A, Dorronsoro A, Scibetta A, Robbins PD, Niedernhofer LJ, Huard J. Inhibition of NF-κB improves the stress resistance and myogenic differentiation of MDSPCs isolated from naturally aged mice. PLoS One. 2017 Jun 22;12(6):e0179270. doi: 10.1371/journal.pone.0179270. eCollection 2017.
Takayama K, Kawakami Y, Lavasani M, Mu X, Cummins JH, Yurube T, Kuroda R, Kurosaka M, Fu FH, Robbins PD, Niedernhofer LJ, Huard J. mTOR signaling plays a critical role in the defects observed in muscle-derived stem/progenitor cells isolated from a murine model of accelerated aging. J Orthop Res. 2017 Jul;35(7):1375-1382. doi: 10.1002/jor.23409. Epub 2016 Sep 22.