Johnny Huard,
PhD
Chief Scientific Officer and Director
Dr. Huard is the Chief Scientific Officer (CSO) and Director of the Center for Regenerative Sports Medicine at the Steadman Philippon Research Institute (SPRI) in Vail, Colorado. Dr. Huard is also an Affiliate Faculty, Department of Clinical and Biomedical Sciences, College of Veterinary Medicine, Colorado State University, Fort Collins Colorado. From 2015-2019, Dr. Huard was Professor, Distinguished Chair in Orthopaedic Research in the Department of Orthopaedic Surgery at the University of Texas Health Science Center at Houston (UTHealth) McGovern Medical School. Between 1995-2015, Dr. Huard held the Henry J. Mankin Endowed Chair in the Department of Orthopaedic Surgery and was the Director of the Stem Cell Research Center (SCRC). Dr. Huard also held numerous secondary appointments at the University of Pittsburgh and was also the Deputy Director for Cellular Therapies at the McGowan Institute for Regenerative Medicine.
Dr. Huard possesses extensive knowledge in the areas of gene therapy, tissue engineering, and regenerative medicine applications based on the use of muscle-derived stem/progenitor cells (MDSCs). The muscle-derived stem cells that his team isolated are currently undergoing testing in clinical trials for treatment of stress urinary incontinence (SUI) and myocardial infarction. More than 700 women suffering with SUI in Canada and the U.S. have volunteered for this stem cell therapy (Phase III Clinical Trial). Dr. Huard and his team have published over 400 peer reviewed papers, over 90 reviews/book chapters, and have over 900 abstracts accepted for presentation at national and international conferences (Citations 39577; h-index:106, i10-index: 340). The major research interests of SPRI’s Center for Regenerative Sports Medicine (CRSM) include: muscle stem cells isolation & characterization; bone & articular cartilage regeneration and repair; alleviation of muscle weakness in Duchenne muscular dystrophy (DMD); cardiac and skeletal muscle injury repair, regeneration, and fibrosis prevention; peripheral nerve regeneration; and the use of adult stem cells as a source for paracrine factors to alleviate the phenotypic changes associated with natural and accelerated aging. The main focus of the Center for Regenerative Sports Medicine laboratory is to develop biological medicine approaches to improve tissue repair after injury, disease and aging. The Huard lab uses a variety of technologies that fall into 4 different categories, including: Biologics (adult stem cells which include muscle derived stem cells, adipose derived stem cells as well as Bone Marrow Aspirate and Platelet Rich Plasma); Regenerative Medicine approaches (gene therapy approaches, CRSPR-Cas9, protein delivery like coacervate, microspheres, PA nanofibers and magnetic nanoparticles); Therapeutics (FDA approved drugs such as anti-fibrotic agents, pro-angiogenic agents, telomerase activity, (hTERT), senolytic and senomorphic drugs); and Animal Modelling (dystrophic and progeria mice models, super healer mice (MRL/MpJ), osteoarthritis model/microfracture, tibia fracture, calvarial defect and ovariectomy).
Current grants:
1) NIH 1UG3AR077748-01 (Huard PI ) 8/1/2020 – 7/31/25
The Use of Senolytic and Anti-Fibrotic Agents to Improve the Beneficial Effect of Bone Marrow Stem Cells for Osteoarthritis.
2) NIH R21 AR072870-01 (Huard PI) 2/27/18-1/31/21
Muscle Stem Cells Reprogrammed Through Genome Engineering for Autonomously Regulated Anti-Fibrotic Therapy.
3) NIH R21 AR073509-01 (Huard PI) 6/01/18 – 5/31/21
Effects of Circulating Factors and Progenitors on Wound Healing during Pregnancy.
4) NIH RO1 AR065445-01 (Huard PI) 5/06/14 – 12/30/20
Bone Abnormalities & Healing Defects in Muscular Dystrophy.
5) DOD N00014-18-RFI-0014 (Huard PI) 10/01/19 - 9/30/22
Office of Naval Research Request for Information (RFI) # N00014-18-RFI-0014. Response to the Treatment of Poly-Traumatic Injuries Using Platelet-Rich Plasma and Bone Marrow Concentrate.
6) NIH 1R21AR075997-01 (Huard, Narkar, Tashman Multi-PI) 8/5/2019-7/31/2021
Development of biological approaches to enhance skeletal muscle rehabilitation after anterior cruciate ligament injury.
7) NIH 1R21AR074132-01A1 (Kolonin, Huard , Multi-PI ) 9/9/2019-7/31-2021
Ablation of Non-Myogenic Progenitor Cells as a New Therapeutic Approach to Duchenne Muscular Dystrophy.
8) DoD N00014-20-S-B001 (Huard, Philippon, Multi-PI) 1/01/2021-12/31/2024
The Use of Senolytic agent to Improve the Benefit of Platelet-Rich Plasma and Losartan for Treatment of Femoroacetabular Impingement and Labral Repair
9) NIH 1 R01 AR077045-01A1(Nakayama, Huard, Multi-PI) 02/01/021-01/31/2026
Articular Cartilage Tissue Engineering with Human Pluripotent Stem Cells
Honors for Dr. Huard’s team.
1) My research has received over 90 honors and awards, both locally and at national/international meetings, including: (A) American Orthopaedic Society for Sports Medicine, Herodicus Award – June, 1997; 3-M Award – June, 1997; Cabaud Award – June, 2000 and 2019; Aircast Award, 2003; Excellence in research award 2019 (B) 4 Orthopaedic Research Society (ORS) New Investigator Recognition Award (NIRA, 2005, 2007, 2011, 2012); (C) Chancellor’s Distinguished Research Award, University of Pittsburgh, 2002; (D) Kappa Delta Young Investigator Award, American Association of Orthopaedic Surgeons – November, 2003; Ortho-Regeneration Award, (ORS 2019).
2) ADDUQAR 2007 Prix d’excellence; docteur honoris causa D.h.c, 2019 F) 4 ASBMR Young Investigator Awards (2 in 2014, 2 in 2018), 6 Merit Based Abstracts Travel Awards (2012, 2014) from American Society of Gene and Cell Therapy.
3) Standing member-NIH Skeletal Muscle and Exercise Physiology Study Section (SMEP) – January 2006-10.
4) Reviewer on numerous NIH study sections (NIAMS Special Emphasis Panel, Small Business Orthopaedic Medicine Special Emphasis Panel, Small Grants for New Investigators (R03), National Institute of Aging, Program Project Proposal, etc.). Reviewer for the Canadian Institute for Health Research, Muscular Dystrophy Association (MDA), Italian Telethon, French Association for Myopathy (AFM), etc.
5) Member - Editorial Board (Molecular Therapy, J. Histology & Histopathology, Cell Transplantation, Tissue Engineering and Regenerative Med., Stem Cells Reviews, Current Genomics), Associate Editor - PloS One.
6) Orthopaedic Research Society: nominating committee (Biologist, 2009), membership committee (Chair, 2013), Program Committee (2015-2017), Chair of the Research Council (2019-2022).
7) University of Pittsburgh Committee for Tenured Faculty Promotions and Appointments (2009-2011).
8) 2018 Kappa Delta Award; American Academy of Orthopaedic Surgeons (AAOS); official award will be presented at the AAOS Annual Meeting, New Orleans, LA, March 8, 2018.
Contributions to Science
1) Duchenne muscular dystrophy (DMD) is a deadly genetic disease characterized by progressive muscle weakness due to a deficiency of dystrophin which usually leads to the loss of independent ambulation by 4-6 years of age, and a fatal outcome due to cardiac or respiratory failure by the third decade. I became very interested in the concept of restoring dystrophin expression to the dystrophin-deficient muscle of DMD patients via the transplantation of normal myoblasts; however, myoblast survival and regeneration capacities were very limited. Eventually, the use of a differential plating technique known as the preplating technique was used to identify a population of muscle-derived stem/progenitor cells that demonstrated high survival and regeneration capacities (1991-2000). DMD patients and animal model also acquire osteopenia, fragility bone fractures, and scoliosis, indicating that other musculoskeletal tissues are affected in DMD. Administration of glucocorticoids remains the gold standard therapy to delay the onset of the DMD pathology, but produces many unwanted side effects including weaker bones. Importantly, DMD patients become wheelchair-bound after they experience a bone fracture, emphasizing the importance of understanding these bone abnormalities in order to develop therapeutics to improve the quality of life of DMD patients. Therefore, we believe that identifying new therapeutic approaches that will work in conjunction with glucocorticoids to improve bone health in DMD patients can have a tremendous therapeutic value for DMD patients (2000-2020).
Huard J, Verreault S, Roy R, Tremblay M, and Tremblay JP. High efficiency of muscle regeneration after human myoblast clone transplantation in SCID mice. J Clin Invest 1994 Feb; 93(2):586-99. PMID: 8113396
Qu Z, Balkir L, Van Deutekom JC, Robbins PD, Pruchnic R, and Huard J. Development of approaches to improve cell survival in myoblast transfer therapy. J Cell Biol 1998 Sep 7; 142(5):1257-67. PMID:9732286
Isaac C, Wright A, Usas A, Li H, Tang Y, Mu X, Greco N, Dong Q, Vo N, Kang J, Wang B, Huard J. Dystrophin and utrophin "double knockout" dystrophic mice exhibit a spectrum of degenerative musculoskeletal abnormalities. J Orthop Res. 2013;31(3):343-9. Epub 2012/10/26. doi: 10.1002/jor.22236. PubMed PMID: 23097179; PMCID: PMC4108902.
Lu A, Poddar M, Tang Y, Proto JD, Sohn J, Mu X, Oyster N, Wang B, Huard J. Rapid depletion of muscle progenitor cells in dystrophic mdx/utrophin-/- mice. Hum Mol Genet. 2014;23(18):4786-800. Epub 2014/05/02. doi: 10.1093/hmg/ddu194. PubMed PMID: 24781208; PMCID: PMC4140461.
Gao X, Tang Y, Amra S, Sun X, Cui Y, Cheng H, Wang B, Huard J. Systemic Investigation of Bone and Muscle Abnormalities in Dystrophin/Utrophin Double Knockout Mice During Postnatal Development and the Mechanisms. Hum Mol Genet. 2019 May 15;28(10):1738-1751. PMID:30689868
2) Blocking fibrosis to promote tissues repair including skeletal and cardiac muscles, cartilage using different strategies. We are currently have several clinical trials funded by DOD and NIH using losartan for cartilage repair and OA treatment (2019-2020).
a. Utsunomiya H, Gao X, Deng Z, Cheng H, Nakama G, Scibetta AC, Ravuri SK, Goldman JL, Lowe WR, Rodkey WG, Alliston T, Philippon MJ, Huard J. Biologically Regulated Marrow Stimulation by Blocking TGF-β1 With Losartan Oral Administration Results in Hyaline-like Cartilage Repair: A Rabbit Osteochondral Defect Model. Am J Sports Med. 2020 Mar;48(4):974-984. Epub 2020 Feb 6. PMID: 32027515
b. Deng Z, Gao X, Sun X, Amra S, Lu A, Cui Y, Eltzschig HK, Lei G, Huard J. Characterization of articular cartilage homeostasis and the mechanism of superior cartilage regeneration of MRL/MpJ mice. FASEB J. 2019 Aug;33(8):8809-8821. Epub 2019 May 1.PMID: 31042406
c. Kobayashi M, Ota S, Terada S, Kawakami Y, Otsuka T, Fu FH, Huard J. The Combined Use of Losartan and Muscle-Derived Stem Cells Significantly Improves the Functional Recovery of Muscle in a Young Mouse Model of Contusion Injuries. Am J Sports Med. 2016 Dec;44(12):3252-3261. Epub 2016 Aug 8. PMID: 27501834
d. Li Y, Li J, Zhu J, Sun B, Branca M, Tang Y, Foster W, Xiao X, and Huard J. Decorin gene transfer promotes muscle cell differentiation and muscle regeneration. Mol Ther 2007 Sep; 15(9):1616-1622, PMID: 17609657.
e. Li Y, Foster W, Deasy BM, Chan Y, Prisk V, Tang Y, Cummins J, and Huard J. Transforming growth factor- β1 induces the differentiation of myogenic cells into fibrotic cells in injured skeletal muscle: a key event in muscle fibrogenesis. Am J Pathol 2004 Mar; 164(3):1007-19. PMID: 14982854.
f. Murray IR, Gonzalez ZN, Baily J, Dobie R, Wallace RJ, Mackinnon AC, Smith JR, Greenhalgh SN,Thompson AI, Conroy KP, Griggs DW, Ruminski PG, Gray GA, Singh M, Campbell MA, Kendall TJ, Dai J, Li Y, Iredale JP, Simpson H, Huard J, Péault B, Henderson NC (2017) αv integrins on mesenchymal cells critically regulate skeletal and cardiac muscle fibrosis. Nature Communications. . 2017 Oct 24;8(1):1118. doi: 10.1038/s41467-017-01097-z
3) The identification of a population of muscle-derived stem cells (MDSCs) that showed superior survival, engraftment, and regenerative potential compared to myoblasts resulted in in-depth characterization of these cells. The cell population was isolated via the “preplate technique,” which takes advantage of the differential adhesion characteristics of the various cell populations found in skeletal muscle to collagen type 1-coated flasks. The population of MDSCs was isolated in a slowly adhering fraction of cells. These MDSCs express markers of stem cells but also display behaviors such as long-term proliferation, self-renewing ability, and multipotent differentiation. Since these cells have the ability to differentiate into multiple lineages and are highly resistant to stresses, they were tested for their ability to repair a variety of non-muscle tissues. Our research identified cells (endothelial and perivascular cells) within the blood vessel walls as the potential source of these stem/progenitor cells. More importantly, the technique for the isolation of MDSCs was patented and licensed to Cook Myosite, Inc. Cook has successfully been isolating human muscle-derived cells, and has applied these cells in clinical trials to treat over 700 women suffering from stress urinary incontinence (SUI) and also to treat patients who have suffered a myocardial infarction (2000-2014).
a. Zheng B, Cao B, Crisan M, Sun B, Li G, Logar A, Yap S, Pollett JB, Drowley L, Cassino T, Gharaibeh B, Deasy B, Huard J, and Péault B. Prospective identification of myogenic endothelial cells in human skeletal muscle. Nat Biotech 2007 Sep; 25(9):1025-34. J. Huard corresponding author. PMID: 17767154.
b. Gharaibeh B, Lu A, Tebbets J, Zheng B, Feduska J, Crisan M, Péault B, Cummins J, and Huard J. Isolation of slowly adhering cells containing stem cells from murine skeletal muscle by the preplate technique. Nature Protocol 2008; 3(9); 1501-1509, PMID: 18772878.
c. Crisan M, Park TS Casteilla L, Sun B, Zheng B, Yap S, Norotte C, Corselli M, Traas J, Deasy B, Andriolo G, Bühring HJ, Lazzari L, Giacobino JP, Huard J, and Péault B. Perivascular origin of mesenchymal stem cells in multiple human tissues. Cell Stem Cell 2008 Sep 11; 3(3):301-13. PMID: 18786417.
d. Cao B, Zheng B, Jankowski RJ, Kimura S, Ikezawa M, Deasy B, Cummins J, Epperly M, Qu-Petersen Z, and Huard J. Muscle stem cells differentiate into hematopoietic lineages but retain myogenic potential. Nat Cell Biol 2003 Jul; 5(7):640-6. PMID: 15872085.
4) We have done large amount of research by use of MDSCs in tissue engineering and regenerative medicine applications for the musculoskeletal system and bone and cartilage biology. I have many publications in this field.
a. Peng H, Wright V, Usas A, and Huard J. Synergistic enhancement of bone formation and healing by stem cell-expressed VEGF and bone morphogenetic protein-4. J Clin Invest 2002, 110:751-759. PMID:12235106
Lavasani M, Thompson SD, Pollett JB, and Huard J. Human muscle-derived stem/progenitor cells promote functional murine peripheral nerve regeneration. J Clin Invest 2014, 124:1745-1756. PMID:24642464
Matsumoto T, Cooper GM, Gharaibeh B, Meszaros LB, Li G, Usas A, Fu FH, Huard J. Cartilage Repair in a Rat Model of Osteoarthritis Through Intraarticular Transplantation of Muscle-Derived Stem Cells Expressing Bone Morphogenetic Protein 4 and Soluble Flt-1. Arthritis Rheum. 2009 May;60(5):1390-405.PMID:19404941
Gao X, Usas A, Proto JD, and Huard J. Role of donor and host cells in muscle-derived stem cell-mediated bone repair: differentiation vs. paracrine effects. FASEB J. 2014. 28:3792-3809. PMID:24843069
Gao X, Usas A, Tang Y, Lu A, Tan J, Schneppendahl J, Kozemchak AM, Wang B, Cummins JH,Tuan RS, Huard J. A Comparison of Bone Regeneration With Human Mesenchymal Stem Cells and Muscle-Derived Stem Cells and the Critical Role of BMP. Biomaterials. 2014 Aug;35(25):6859-70. PMID:24856105
Gao X, Cheng H, Awada H, Tang Y, Amra S, Lu A, Sun X, Lv G, Huard C, Wang B, Bi X, Wang Y, Huard J. A comparison of BMP2 delivery by coacervate and gene therapy for promoting human muscle-derived stem cell-mediated articular cartilage repair. Stem Cell Res Ther. 2019 Nov 26;10(1):346. PMID: 31771623
5) More recently, we have observed that stem cell depletion/exhaustion occurs during natural and accelerated aging as well as during the rapid progression of the disease in muscular dystrophy. We have also observed that transplantation of young MDSCs can be used to delay aging and the progression of diseases, such as muscular dystrophy. The mechanisms by which these cells delay aging and disease progress has been attributed to the potent paracrine effects of MDSCs in a variety of tissues (2012-2015).
a. Mu X, Tseng C, Hambright WS, Matre P, Lin CY, Chanda P, Chen W, Gu J, Ravuri S, Cui Y, Zhong L, Cooke JP, Niedernhofer LJ, Robbins PD, Huard J. Cytoskeleton stiffness regulates cellular senescence and innate immune response in Hutchinson-Gilford Progeria Syndrome. Aging Cell. 2020 Jul 25;19(8):e13152.PMID: 32710480
b. Lavasani M, Robinson A, Lu A, Song M, Feduska J, Ahani B, Tilstra J, Feldman C, Robbins P, Niedernhofer L, and Huard J. Muscle-derived stem cell dysfunction limits healthspan and lifespan in a murine progeria model. Nat Commun 2012 Jan; 3:608. PMID: 22215083.
c. Song M, Lavasani M, Thompson SD, Lu A, Ahani B, and Huard J. Muscle-derived stem/progenitor cell dysfunction in Zmpste24-deficient progeroid mice limits muscle regeneration. Stem Cell Res Ther 2013 Mar 25; 4(2):33. PMID: 23531345.
d. Mu X, Usas A, Tang Y, Lu A, Wang B, Weiss K, and Huard J. RhoA mediates defective stem cell function and heterotopic ossification in dystrophic muscle of mice. FASEB J 2013 Sep; 27(9):3619-31.PMID: 23704088.
e. Mu X, Tang Y, Takayama K, Chen W, Lu A, Wang B, Weiss K, Huard J. RhoA/ROCK inhibition improves the beneficial effects of glucocorticoid treatment in dystrophic muscle: implications for stem cell depletion. Hum Mol Genet. 2017 Aug 1;26(15):2813-2824.PMID: 28549178.
f. Yousefzadeh MJ, Flores RR, Zhu Y, Schmiechen ZC, Brooks RW, Trusson CE, Cui Y, Angelini LA, Lee KA, McGowan SJ, Burrack AL, Wang D, Lu A, Sano T, O’Kelly RD, Pillai SPS, Klug J, Ladiges WL, Burd CE, Lewis SE, LaRusso NF, Vo NV, Wang Y, Kelley EE, Huard J, Stromnes IM, Robbins PD, Niedernhofer LJ. An aged immune system drives senescence and aging of solid organs. Nature, December 2020. (Accepted for publication).
Complete List of Published Work in My Bibliography (over 400 papers):
https://pubmed.ncbi.nlm.nih.gov/?term=Huard+J&sort=pubdate
https://scholar.google.com/citations?hl=en&user=cKSullEAAAAJ
Dr. Huard possesses extensive knowledge in the areas of gene therapy, tissue engineering, and regenerative medicine applications based on the use of muscle-derived stem/progenitor cells (MDSCs). The muscle-derived stem cells that his team isolated are currently undergoing testing in clinical trials for treatment of stress urinary incontinence (SUI) and myocardial infarction. More than 700 women suffering with SUI in Canada and the U.S. have volunteered for this stem cell therapy (Phase III Clinical Trial). Dr. Huard and his team have published over 400 peer reviewed papers, over 90 reviews/book chapters, and have over 900 abstracts accepted for presentation at national and international conferences (Citations 39577; h-index:106, i10-index: 340). The major research interests of SPRI’s Center for Regenerative Sports Medicine (CRSM) include: muscle stem cells isolation & characterization; bone & articular cartilage regeneration and repair; alleviation of muscle weakness in Duchenne muscular dystrophy (DMD); cardiac and skeletal muscle injury repair, regeneration, and fibrosis prevention; peripheral nerve regeneration; and the use of adult stem cells as a source for paracrine factors to alleviate the phenotypic changes associated with natural and accelerated aging. The main focus of the Center for Regenerative Sports Medicine laboratory is to develop biological medicine approaches to improve tissue repair after injury, disease and aging. The Huard lab uses a variety of technologies that fall into 4 different categories, including: Biologics (adult stem cells which include muscle derived stem cells, adipose derived stem cells as well as Bone Marrow Aspirate and Platelet Rich Plasma); Regenerative Medicine approaches (gene therapy approaches, CRSPR-Cas9, protein delivery like coacervate, microspheres, PA nanofibers and magnetic nanoparticles); Therapeutics (FDA approved drugs such as anti-fibrotic agents, pro-angiogenic agents, telomerase activity, (hTERT), senolytic and senomorphic drugs); and Animal Modelling (dystrophic and progeria mice models, super healer mice (MRL/MpJ), osteoarthritis model/microfracture, tibia fracture, calvarial defect and ovariectomy).
Current grants:
1) NIH 1UG3AR077748-01 (Huard PI ) 8/1/2020 – 7/31/25
The Use of Senolytic and Anti-Fibrotic Agents to Improve the Beneficial Effect of Bone Marrow Stem Cells for Osteoarthritis.
2) NIH R21 AR072870-01 (Huard PI) 2/27/18-1/31/21
Muscle Stem Cells Reprogrammed Through Genome Engineering for Autonomously Regulated Anti-Fibrotic Therapy.
3) NIH R21 AR073509-01 (Huard PI) 6/01/18 – 5/31/21
Effects of Circulating Factors and Progenitors on Wound Healing during Pregnancy.
4) NIH RO1 AR065445-01 (Huard PI) 5/06/14 – 12/30/20
Bone Abnormalities & Healing Defects in Muscular Dystrophy.
5) DOD N00014-18-RFI-0014 (Huard PI) 10/01/19 - 9/30/22
Office of Naval Research Request for Information (RFI) # N00014-18-RFI-0014. Response to the Treatment of Poly-Traumatic Injuries Using Platelet-Rich Plasma and Bone Marrow Concentrate.
6) NIH 1R21AR075997-01 (Huard, Narkar, Tashman Multi-PI) 8/5/2019-7/31/2021
Development of biological approaches to enhance skeletal muscle rehabilitation after anterior cruciate ligament injury.
7) NIH 1R21AR074132-01A1 (Kolonin, Huard , Multi-PI ) 9/9/2019-7/31-2021
Ablation of Non-Myogenic Progenitor Cells as a New Therapeutic Approach to Duchenne Muscular Dystrophy.
8) DoD N00014-20-S-B001 (Huard, Philippon, Multi-PI) 1/01/2021-12/31/2024
The Use of Senolytic agent to Improve the Benefit of Platelet-Rich Plasma and Losartan for Treatment of Femoroacetabular Impingement and Labral Repair
9) NIH 1 R01 AR077045-01A1(Nakayama, Huard, Multi-PI) 02/01/021-01/31/2026
Articular Cartilage Tissue Engineering with Human Pluripotent Stem Cells
Honors for Dr. Huard’s team.
1) My research has received over 90 honors and awards, both locally and at national/international meetings, including: (A) American Orthopaedic Society for Sports Medicine, Herodicus Award – June, 1997; 3-M Award – June, 1997; Cabaud Award – June, 2000 and 2019; Aircast Award, 2003; Excellence in research award 2019 (B) 4 Orthopaedic Research Society (ORS) New Investigator Recognition Award (NIRA, 2005, 2007, 2011, 2012); (C) Chancellor’s Distinguished Research Award, University of Pittsburgh, 2002; (D) Kappa Delta Young Investigator Award, American Association of Orthopaedic Surgeons – November, 2003; Ortho-Regeneration Award, (ORS 2019).
2) ADDUQAR 2007 Prix d’excellence; docteur honoris causa D.h.c, 2019 F) 4 ASBMR Young Investigator Awards (2 in 2014, 2 in 2018), 6 Merit Based Abstracts Travel Awards (2012, 2014) from American Society of Gene and Cell Therapy.
3) Standing member-NIH Skeletal Muscle and Exercise Physiology Study Section (SMEP) – January 2006-10.
4) Reviewer on numerous NIH study sections (NIAMS Special Emphasis Panel, Small Business Orthopaedic Medicine Special Emphasis Panel, Small Grants for New Investigators (R03), National Institute of Aging, Program Project Proposal, etc.). Reviewer for the Canadian Institute for Health Research, Muscular Dystrophy Association (MDA), Italian Telethon, French Association for Myopathy (AFM), etc.
5) Member - Editorial Board (Molecular Therapy, J. Histology & Histopathology, Cell Transplantation, Tissue Engineering and Regenerative Med., Stem Cells Reviews, Current Genomics), Associate Editor - PloS One.
6) Orthopaedic Research Society: nominating committee (Biologist, 2009), membership committee (Chair, 2013), Program Committee (2015-2017), Chair of the Research Council (2019-2022).
7) University of Pittsburgh Committee for Tenured Faculty Promotions and Appointments (2009-2011).
8) 2018 Kappa Delta Award; American Academy of Orthopaedic Surgeons (AAOS); official award will be presented at the AAOS Annual Meeting, New Orleans, LA, March 8, 2018.
Contributions to Science
1) Duchenne muscular dystrophy (DMD) is a deadly genetic disease characterized by progressive muscle weakness due to a deficiency of dystrophin which usually leads to the loss of independent ambulation by 4-6 years of age, and a fatal outcome due to cardiac or respiratory failure by the third decade. I became very interested in the concept of restoring dystrophin expression to the dystrophin-deficient muscle of DMD patients via the transplantation of normal myoblasts; however, myoblast survival and regeneration capacities were very limited. Eventually, the use of a differential plating technique known as the preplating technique was used to identify a population of muscle-derived stem/progenitor cells that demonstrated high survival and regeneration capacities (1991-2000). DMD patients and animal model also acquire osteopenia, fragility bone fractures, and scoliosis, indicating that other musculoskeletal tissues are affected in DMD. Administration of glucocorticoids remains the gold standard therapy to delay the onset of the DMD pathology, but produces many unwanted side effects including weaker bones. Importantly, DMD patients become wheelchair-bound after they experience a bone fracture, emphasizing the importance of understanding these bone abnormalities in order to develop therapeutics to improve the quality of life of DMD patients. Therefore, we believe that identifying new therapeutic approaches that will work in conjunction with glucocorticoids to improve bone health in DMD patients can have a tremendous therapeutic value for DMD patients (2000-2020).
Huard J, Verreault S, Roy R, Tremblay M, and Tremblay JP. High efficiency of muscle regeneration after human myoblast clone transplantation in SCID mice. J Clin Invest 1994 Feb; 93(2):586-99. PMID: 8113396
Qu Z, Balkir L, Van Deutekom JC, Robbins PD, Pruchnic R, and Huard J. Development of approaches to improve cell survival in myoblast transfer therapy. J Cell Biol 1998 Sep 7; 142(5):1257-67. PMID:9732286
Isaac C, Wright A, Usas A, Li H, Tang Y, Mu X, Greco N, Dong Q, Vo N, Kang J, Wang B, Huard J. Dystrophin and utrophin "double knockout" dystrophic mice exhibit a spectrum of degenerative musculoskeletal abnormalities. J Orthop Res. 2013;31(3):343-9. Epub 2012/10/26. doi: 10.1002/jor.22236. PubMed PMID: 23097179; PMCID: PMC4108902.
Lu A, Poddar M, Tang Y, Proto JD, Sohn J, Mu X, Oyster N, Wang B, Huard J. Rapid depletion of muscle progenitor cells in dystrophic mdx/utrophin-/- mice. Hum Mol Genet. 2014;23(18):4786-800. Epub 2014/05/02. doi: 10.1093/hmg/ddu194. PubMed PMID: 24781208; PMCID: PMC4140461.
Gao X, Tang Y, Amra S, Sun X, Cui Y, Cheng H, Wang B, Huard J. Systemic Investigation of Bone and Muscle Abnormalities in Dystrophin/Utrophin Double Knockout Mice During Postnatal Development and the Mechanisms. Hum Mol Genet. 2019 May 15;28(10):1738-1751. PMID:30689868
2) Blocking fibrosis to promote tissues repair including skeletal and cardiac muscles, cartilage using different strategies. We are currently have several clinical trials funded by DOD and NIH using losartan for cartilage repair and OA treatment (2019-2020).
a. Utsunomiya H, Gao X, Deng Z, Cheng H, Nakama G, Scibetta AC, Ravuri SK, Goldman JL, Lowe WR, Rodkey WG, Alliston T, Philippon MJ, Huard J. Biologically Regulated Marrow Stimulation by Blocking TGF-β1 With Losartan Oral Administration Results in Hyaline-like Cartilage Repair: A Rabbit Osteochondral Defect Model. Am J Sports Med. 2020 Mar;48(4):974-984. Epub 2020 Feb 6. PMID: 32027515
b. Deng Z, Gao X, Sun X, Amra S, Lu A, Cui Y, Eltzschig HK, Lei G, Huard J. Characterization of articular cartilage homeostasis and the mechanism of superior cartilage regeneration of MRL/MpJ mice. FASEB J. 2019 Aug;33(8):8809-8821. Epub 2019 May 1.PMID: 31042406
c. Kobayashi M, Ota S, Terada S, Kawakami Y, Otsuka T, Fu FH, Huard J. The Combined Use of Losartan and Muscle-Derived Stem Cells Significantly Improves the Functional Recovery of Muscle in a Young Mouse Model of Contusion Injuries. Am J Sports Med. 2016 Dec;44(12):3252-3261. Epub 2016 Aug 8. PMID: 27501834
d. Li Y, Li J, Zhu J, Sun B, Branca M, Tang Y, Foster W, Xiao X, and Huard J. Decorin gene transfer promotes muscle cell differentiation and muscle regeneration. Mol Ther 2007 Sep; 15(9):1616-1622, PMID: 17609657.
e. Li Y, Foster W, Deasy BM, Chan Y, Prisk V, Tang Y, Cummins J, and Huard J. Transforming growth factor- β1 induces the differentiation of myogenic cells into fibrotic cells in injured skeletal muscle: a key event in muscle fibrogenesis. Am J Pathol 2004 Mar; 164(3):1007-19. PMID: 14982854.
f. Murray IR, Gonzalez ZN, Baily J, Dobie R, Wallace RJ, Mackinnon AC, Smith JR, Greenhalgh SN,Thompson AI, Conroy KP, Griggs DW, Ruminski PG, Gray GA, Singh M, Campbell MA, Kendall TJ, Dai J, Li Y, Iredale JP, Simpson H, Huard J, Péault B, Henderson NC (2017) αv integrins on mesenchymal cells critically regulate skeletal and cardiac muscle fibrosis. Nature Communications. . 2017 Oct 24;8(1):1118. doi: 10.1038/s41467-017-01097-z
3) The identification of a population of muscle-derived stem cells (MDSCs) that showed superior survival, engraftment, and regenerative potential compared to myoblasts resulted in in-depth characterization of these cells. The cell population was isolated via the “preplate technique,” which takes advantage of the differential adhesion characteristics of the various cell populations found in skeletal muscle to collagen type 1-coated flasks. The population of MDSCs was isolated in a slowly adhering fraction of cells. These MDSCs express markers of stem cells but also display behaviors such as long-term proliferation, self-renewing ability, and multipotent differentiation. Since these cells have the ability to differentiate into multiple lineages and are highly resistant to stresses, they were tested for their ability to repair a variety of non-muscle tissues. Our research identified cells (endothelial and perivascular cells) within the blood vessel walls as the potential source of these stem/progenitor cells. More importantly, the technique for the isolation of MDSCs was patented and licensed to Cook Myosite, Inc. Cook has successfully been isolating human muscle-derived cells, and has applied these cells in clinical trials to treat over 700 women suffering from stress urinary incontinence (SUI) and also to treat patients who have suffered a myocardial infarction (2000-2014).
a. Zheng B, Cao B, Crisan M, Sun B, Li G, Logar A, Yap S, Pollett JB, Drowley L, Cassino T, Gharaibeh B, Deasy B, Huard J, and Péault B. Prospective identification of myogenic endothelial cells in human skeletal muscle. Nat Biotech 2007 Sep; 25(9):1025-34. J. Huard corresponding author. PMID: 17767154.
b. Gharaibeh B, Lu A, Tebbets J, Zheng B, Feduska J, Crisan M, Péault B, Cummins J, and Huard J. Isolation of slowly adhering cells containing stem cells from murine skeletal muscle by the preplate technique. Nature Protocol 2008; 3(9); 1501-1509, PMID: 18772878.
c. Crisan M, Park TS Casteilla L, Sun B, Zheng B, Yap S, Norotte C, Corselli M, Traas J, Deasy B, Andriolo G, Bühring HJ, Lazzari L, Giacobino JP, Huard J, and Péault B. Perivascular origin of mesenchymal stem cells in multiple human tissues. Cell Stem Cell 2008 Sep 11; 3(3):301-13. PMID: 18786417.
d. Cao B, Zheng B, Jankowski RJ, Kimura S, Ikezawa M, Deasy B, Cummins J, Epperly M, Qu-Petersen Z, and Huard J. Muscle stem cells differentiate into hematopoietic lineages but retain myogenic potential. Nat Cell Biol 2003 Jul; 5(7):640-6. PMID: 15872085.
4) We have done large amount of research by use of MDSCs in tissue engineering and regenerative medicine applications for the musculoskeletal system and bone and cartilage biology. I have many publications in this field.
a. Peng H, Wright V, Usas A, and Huard J. Synergistic enhancement of bone formation and healing by stem cell-expressed VEGF and bone morphogenetic protein-4. J Clin Invest 2002, 110:751-759. PMID:12235106
Lavasani M, Thompson SD, Pollett JB, and Huard J. Human muscle-derived stem/progenitor cells promote functional murine peripheral nerve regeneration. J Clin Invest 2014, 124:1745-1756. PMID:24642464
Matsumoto T, Cooper GM, Gharaibeh B, Meszaros LB, Li G, Usas A, Fu FH, Huard J. Cartilage Repair in a Rat Model of Osteoarthritis Through Intraarticular Transplantation of Muscle-Derived Stem Cells Expressing Bone Morphogenetic Protein 4 and Soluble Flt-1. Arthritis Rheum. 2009 May;60(5):1390-405.PMID:19404941
Gao X, Usas A, Proto JD, and Huard J. Role of donor and host cells in muscle-derived stem cell-mediated bone repair: differentiation vs. paracrine effects. FASEB J. 2014. 28:3792-3809. PMID:24843069
Gao X, Usas A, Tang Y, Lu A, Tan J, Schneppendahl J, Kozemchak AM, Wang B, Cummins JH,Tuan RS, Huard J. A Comparison of Bone Regeneration With Human Mesenchymal Stem Cells and Muscle-Derived Stem Cells and the Critical Role of BMP. Biomaterials. 2014 Aug;35(25):6859-70. PMID:24856105
Gao X, Cheng H, Awada H, Tang Y, Amra S, Lu A, Sun X, Lv G, Huard C, Wang B, Bi X, Wang Y, Huard J. A comparison of BMP2 delivery by coacervate and gene therapy for promoting human muscle-derived stem cell-mediated articular cartilage repair. Stem Cell Res Ther. 2019 Nov 26;10(1):346. PMID: 31771623
5) More recently, we have observed that stem cell depletion/exhaustion occurs during natural and accelerated aging as well as during the rapid progression of the disease in muscular dystrophy. We have also observed that transplantation of young MDSCs can be used to delay aging and the progression of diseases, such as muscular dystrophy. The mechanisms by which these cells delay aging and disease progress has been attributed to the potent paracrine effects of MDSCs in a variety of tissues (2012-2015).
a. Mu X, Tseng C, Hambright WS, Matre P, Lin CY, Chanda P, Chen W, Gu J, Ravuri S, Cui Y, Zhong L, Cooke JP, Niedernhofer LJ, Robbins PD, Huard J. Cytoskeleton stiffness regulates cellular senescence and innate immune response in Hutchinson-Gilford Progeria Syndrome. Aging Cell. 2020 Jul 25;19(8):e13152.PMID: 32710480
b. Lavasani M, Robinson A, Lu A, Song M, Feduska J, Ahani B, Tilstra J, Feldman C, Robbins P, Niedernhofer L, and Huard J. Muscle-derived stem cell dysfunction limits healthspan and lifespan in a murine progeria model. Nat Commun 2012 Jan; 3:608. PMID: 22215083.
c. Song M, Lavasani M, Thompson SD, Lu A, Ahani B, and Huard J. Muscle-derived stem/progenitor cell dysfunction in Zmpste24-deficient progeroid mice limits muscle regeneration. Stem Cell Res Ther 2013 Mar 25; 4(2):33. PMID: 23531345.
d. Mu X, Usas A, Tang Y, Lu A, Wang B, Weiss K, and Huard J. RhoA mediates defective stem cell function and heterotopic ossification in dystrophic muscle of mice. FASEB J 2013 Sep; 27(9):3619-31.PMID: 23704088.
e. Mu X, Tang Y, Takayama K, Chen W, Lu A, Wang B, Weiss K, Huard J. RhoA/ROCK inhibition improves the beneficial effects of glucocorticoid treatment in dystrophic muscle: implications for stem cell depletion. Hum Mol Genet. 2017 Aug 1;26(15):2813-2824.PMID: 28549178.
f. Yousefzadeh MJ, Flores RR, Zhu Y, Schmiechen ZC, Brooks RW, Trusson CE, Cui Y, Angelini LA, Lee KA, McGowan SJ, Burrack AL, Wang D, Lu A, Sano T, O’Kelly RD, Pillai SPS, Klug J, Ladiges WL, Burd CE, Lewis SE, LaRusso NF, Vo NV, Wang Y, Kelley EE, Huard J, Stromnes IM, Robbins PD, Niedernhofer LJ. An aged immune system drives senescence and aging of solid organs. Nature, December 2020. (Accepted for publication).
Complete List of Published Work in My Bibliography (over 400 papers):
https://pubmed.ncbi.nlm.nih.gov/?term=Huard+J&sort=pubdate
https://scholar.google.com/citations?hl=en&user=cKSullEAAAAJ