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Dr. Sanjiv Dhingra

Dr. Sanjiv Dhingra

Principal Investigator
Cardiac Regeneration and Tissue Engineering Program, Institute of Cardiovascular Sciences

Professor
Regenerative Medicine Program, Department of Physiology and Pathophysiology, University of Manitoba

Research Focus

Dr. Dhingra’s laboratory focuses on various aspects of cardiac regeneration and myocardial tissue engineering using stem cell-based and biomaterials-based approaches to restore function following a cardiac injury. Clinical translation of stem cell-based approaches depends upon in-depth knowledge of the donor stem cell and it is very important to develop a strong understanding of the survival pattern of donor cells following transplantation in the injured myocardium.

Dr. Dhingra’s immediate interests are to investigate the basic mechanisms of immune rejection of transplanted allogeneic (unrelated donor) mesenchymal stem cells (MSCs), embryonic stem (ES) cells, induced pluripotent stem (iPS) cells in the heart in order to develop strategies to enhance the survival of these cells and successfully repair damaged myocardium. He is also interested in developing clinically relevant biomaterials for myocardial tissue engineering and developing strategies to increase host immune tolerance to prevent the rejection of biodegradable patches and scaffolds seeded with stem cells and implanted into the injured heart.

Why is this work important?

Patient-derived autologous stem cells have been demonstrated to be safe and effective for cardiac repair. In preclinical studies conducted in young animals, the transplanted MSCs significantly improved cardiac function after acute or chronic myocardial infarction (MI). However, the initial clinical trials with autologous MSCs in ageing patients suggested only marginal beneficial effects on heart function. The difference between the preclinical and clinical trials was largely due to an age-related decrease in the proliferation and regenerative capability of MSCs from aged patients compared to healthy young animal donors. Unfortunately, the risk of congestive heart failure (CHF) rises with increasing age due to the malfunction of the angiogenic repair mechanisms and several other reasons. Thus, a source of highly regenerative donor stem cells would dramatically improve the ability of stem cell therapy to prevent CHF in older, debilitated patients. To this end, allogeneic stem cells isolated from healthy, young volunteers are good candidate cells for cardiac regeneration and repair. However, the long-term ability of allogeneic cell therapy to preserve heart function is limited because very few allogeneic cells escape the host immune response and survive in the myocardium. Various studies using different cell types have reported that the improvement in heart function was found to be proportional to the number of implanted cells surviving in the myocardium. Hence, the development of new strategies to suppress host immune responses and enhance the survival of transplanted allogeneic cells could have a tremendous impact on the outcome of stem cell therapy for cardiac repair and regeneration.

What techniques and equipment are used in this laboratory?

This laboratory has techniques as well as tools to isolate and culture different stem cell populations and transplant these cells to the infarct area after inducing myocardial infarction in various animal models; combining stem cell biology and molecular biology techniques to accomplish research goals.

About Dr. Sanjiv Dhingra

Dr. Sanjiv Dhingra is a Professor in the Regenerative Medicine Program, Department of Physiology, University of Manitoba. Prior to joining as a faculty member at the University of Manitoba, Dr. Dhingra received postdoctoral training at McEwen Centre for Regenerative Medicine, Toronto General Hospital and at the Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre in Winnipeg. He received postdoctoral fellowship awards from CIHR and MHRC with high rankings. In October 2007, Dr. Dhingra received an award from the Life Science Association of Manitoba for his contribution to cardiovascular research. In May 2010 he received the Early Career Investigator Award from the International Society of Heart Research in Kyoto, Japan. Recently, Dr. Dhingra was a finalist for the Vivien Thomas Young Investigator Award at American Heart Association Scientific Sessions in Los Angeles. In addition to his research program, Dr. Dhingra is also responsible for directing the Canada Italy Tissue Engineering Laboratory (CITEL), a collaboration between the University of Rome “Tor Vergata” and the Institute of Cardiovascular Sciences, St. Boniface Research Centre. Under his supervision, CITEL will develop innovative technologies for biomaterials and will define pioneering procedures for cardiac tissue engineering.

For more information, contact:

Dr. Sanjiv Dhingra
Office. (204) 235-3454
Lab. (204) 235-3648
Fax. 204-233-6723
sdhingra@sbrc.ca

Assistant: Katie Bak
Tel. (204) 235-3648
kbak@sbrc.ca

St. Boniface Hospital Research
R3028-2, 351 Taché Avenue,
Winnipeg, MB
R2H 2A6

In Detail

Preventing the rejection of allogeneic stem cells

Allogeneic stem cells offer several advantages over autologous cells, including excellent regenerative potential, immediate availability for clinical application. In various pre-clinical and clinical studies allogeneic mesenchymal stromal cells (MSCs), embryonic stem (ES) cells or induced pluripotent stem (iPS) cells have been demonstrated to engraft in the infarcted heart, differentiate into different cell types of cardiac lineage and induce cardiac repair. However in all these studies the long-term fate of the cells in the recipient myocardium was not assessed. We recently observed that after implantation, differentiation of allogeneic mesenchymal stem cells within the infarcted myocardium results in the loss of their immunoprivilege and rejection of these cells by the heart and progressive deterioration of ventricular function. Also in various pre-clinical models allogeneic embryonic stem cells and iPS implanted into different disease models were recognized by recipient immune system and rejected. Thus, an in-depth investigation of the immune characteristics of allogeneic stem cells and their interaction with the recipient immune system seems necessary to prevent the rejection of transplanted allogeneic cells and to improve their efficacy for cardiac repair.

My research program investigates the effect of stem cell differentiation on their immunogenicity. We use pharmacological and genetic interventions to study the molecular mechanisms responsible for alterations that lead to changes in the immune characteristics of stem cells following differentiation. This will help us in designing the strategies to preserve immunoprivilege of allogeneic stem cells. I believe that the benefit of current stem cell therapy based approaches to restore ventricular function after an extensive MI would be greatly enhanced if the cells could be rendered immunoprivileged. The studies have suggested that immunosenescence is a barrier to transplant tolerance and the changes associated with the process of ageing create a barrier to tolerance for allograft. Thus another approach that I want to use to prevent rejection of allogeneic stem cells in the injured myocardium will be to increase the immune tolerance in aged recipients by targeting the cytotoxic T cell activation pathways, and by regulatory T cell induction. This will help in designing new therapies to promote immune tolerance and cell survival.

Tissue Engineering

My laboratory also aims to develop clinically relevant and robust technologies to discover biomaterials for cardiac tissue engineering. Our long-term goals in this direction are to engineer tissue grafts for application in cardiac regenerative medicine. Biological scaffold materials currently being used for cardiac tissue engineering are made from different animal, tissue and cell sources, raising concerns about the effect of the immune response to biomaterials. Commonly used commercial products are derived from both allogeneic and xenogeneic sources and allo-immune responses by the recipients against these materials have not been investigated thoroughly. Basically the allogeneic and xenogeneic surface antigens and epitopes present in the biomaterials are thought to contribute to the host immune responses. Our focus is to develop an in-depth understanding of the host immune responses against biomaterials and the strategies to increase host immune tolerance to prevent the rejection of biodegradable patches and scaffolds implanted into the injured heart.

  1. Srivastava* A, Rafieerad A*, Yan W, Alagarsamy KN, Sareen N, Regi LR, Aliani M, Dhingra S. (2024). Germanane quantum dots promote metabolic reprogramming of immune cells towards regulatory T cells and suppress inflammation in vitro and in vivo. Advanced materials, (In revision). (Impact factor: 29.4).
  1. Gill JK, Rehasia SK, Sareen N, Verma E, Dhingra S. (2024) Stem cell therapy for cardiac regeneration: Past, Present and Future. Canadian J Physiol Pharmacol. doi: 10.1139/cjpp-2023.
  1. Rafieerad A*, Saleth LR*, Khanahmadi S, Amiri A, Alagarsamy KN, Dhingra S. (2024) Periodic Table of Immunomodulatory Elements and Derived Two-Dimensional Biomaterials. Progress in Material Science. (Invited, Submitted). (Impact factor: 37.4)
  1. Shojaei S, Basso J, Amereh M, Alizadeh J, Dehesh T, De Silva Rosa S, Clark C, Hassa M, Tomczyk M, Cole L, Hatch G, Dolinsky V, Pasco C, Schibli D, Dhingra S, Srivastava A, Ravandi A, Vitorino R, Ghavami G, Akbari M. (2024). A multi-omics analysis of glioma chemoresistance using a hybrid microphysiological model of glioblastoma. Nature Communications (Impact factor: 17.6). (In revision).

2023

  1. Yan W*, Rafieerad A*, Alagarsamy KN, Saleth LR, Arora RC, Dhingra S. (2023). Immunoengineered MXene Nanosystem for Mitigation of Alloantigen Presentation and Prevention of Transplant Vasculopathy. Nano Today, 48, February, 101706. (Impact factor: 18.9).
  1. Sareen N, Srivastava A, Lionetti V, Dhingra S. (2023) Stem cells derived exosomes and biomaterials to modulate autophagy and mend broken hearts. BBA – Mole Basis of Dis. July 10, 1869(7)166806. (Impact factor: 6.2).
  2. Sharma P, Kaushal N, Saleth LR, Ghavami S, Dhingra S, Kaur P. (2023). Oxidative stress-induced apoptosis and autophagy: Balancing the contrary forces in spermatogenesis. BBA – Mole Basis of Dis. May 3;166742. doi: 10.1016/j.bbadis.2023.166742
  1. Yilmazer A, Alagarsamy KN, Gokce C, Summak GY, Rafieerad A, Bayrakdar F, Ozturk BI, Aktuna S, Delogu, LG, Unal MA, Dhingra S. (2023). Low dose of Ti3C2 MXene quantum dots mitigate SARS-CoV2 infection. Small Methods (Impact factor: 15.4). 19;e2300044:doi”10.1002/smtd.202300044.

2022

  1. Sequiera GL*, Srivastava* A, Sareen N, Yan W, Alagarsamy KN, Verma E, Aghanoori MR, Aliani M, Kumar A, Fernyhough P, Rockman-Greenberg C, Dhingra S. (2022). Development of iPSC-based clinical trial suitability platform for patients with ultra-rare diseases. Science Advances (Impact factor: 14.9). 2022 Apr 8;8(14):eabl4370. doi: 10.1126/sciadv.abl4370.
  1. Rafieerad A, Amiri A, Yan W, Eshghi H, Dhingra S. (2022). Conversion of 2D MXene to multi-low-dimensional GerMXene superlattice heterostructure. Advanced Functional Materials, March 2;32(10): 2108495: doi/adfm.2021108495. (Impact factor: 19.9).
  1. Dhingra R, Rabinovich-Nikitin I, Guberman M, Margulets V, Alagarsamy KN, Aguilar F, Gang H, Jassal D, Dhingra S, Kirshenbaum LA. (2022). Proteasomal Degradation of TRAF2 Mediates Mitochondrial Dysfunction in Doxorubicin-Cardiomyopathy. Circulation (Impact factor: 39.9). August 19: doi: 10.1161/121.058
  1. Srivastava A, Siwach I, Rockman-Greenberg C, Dhingra S. (2022) Reprogramming of hypophosphatasia patient cells to generate a new human iPSC cell line (UOMi009-A). Stem Cell Res. Oct 64:102921. doi: 10.1016/j.scr.2022.102921.
  1. Khanahmadi S, Rafieerad A, Richter C, Dhingra S, Moerschbacher B. (2022). Ti3C2Tx MXene nanosheets enhance systemic plant disease resistance. Nano Today (Impact factor: 20.72). Revision Requested.
  1. Bashnadeh K, Amiri A, Rafieerad A, Rahman MS, Yan W, Dhingra S, Ploycarpou A. (2022) MXene-aromatic thermosetting copolyester nanocomposite as an extremely wear-resistant biocompatible implant material for osteoarthritis applications. July 2022. App. Surface Science. 600(8):154124.
  1. Srivastava A, Verma E, Rockman-Greenberg C, Dhingra S. (2022) Generation of a new human iPSC cell line (UOMi008-A) from a hypophosphatasia patient. Stem Cell Res. Aug 9;64:102891. doi: 10.1016/j.scr.2022.102891.
  1. Adelipour M, Saleth LR, Ghavami S, Alagarsamy KN, Dhingra S, Allameh A. (2022). The role autophagy in the regulation of stem cell growth and differentiation. BBA- Mol. Basis of Dis. Aug 1;1868(8):166412. doi: 10.1016/j.bbadis.2022.166412
  1. Srivastava A, Sareen N, Lionetti V, Rockman-Greenberg C, Dhingra S. (2022). An insight into the mechanisms of COVID-19 infection severity in diabetic patients and possible treatment strategies. Mol, Cellular Biochemistry. March 2:1-15. doi: 10.1007/s11010-022-04396-2.
  1. Srivastava A, Jaryal R, Rockman-Greenberg C, Dhingra S. (2022) Establishment of a new human iPSC cell line (UOMi007-A) line from a patient with hypophosphatasia. Stem Cell Res. Aug;63:102839. doi: 10.1016/j.scr.2022.102839
  1. Lionetti V, Sareen N, Dhingra S. (2022). The analysis of nanovesicles, biomaterials and chemical compounds: Assisting the promotion of angiogenesis and enhancing tissue engineering strategies. Front. Cardiovasc. Med. 2022 Apr 26;9:904738. doi: 10.3389/fcvm.2022.904738.

 

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2012, Vivien Thomas Young Investigator Award (Finalist) (AHA Scientific Sessions, Los Angeles)

2011, Travel Award Winnipeg Heart International Conference, Winnipeg

2011, Stem Cell Network of Canada-Pfizer’s See the Potential Postdoctoral Fellowship Finalist in 2011competition

2011, Finalist, Young Investigator Award, Winnipeg Heart International Conference

2010, Early Career Investigator Award, ISHR, XXth World Heart Congress, Kyoto, Japan

2009, CIHR-RPP Postdoctoral Fellowship

2009, Best Oral Presentation Award, 5th Cardiac Sciences Resident Research Symposium,

2009, Travel Award, 1st Cuba-Canada International Heart Symposium, Holguin

2008, CIHR, Heart & Stroke Foundation-IMPACT Postdoctoral Fellowship

2008, Dr. Arnold Naimark, Young Investigator Award, Institute of Cardiovascular Sciences, University of Manitoba

2008, Junior Scientist Award in Physiology, Federation of American Societies for Experimental Biology, San Diego, USA

2007, Manitoba Health Research Council, Postdoctoral Fellowship (Application ranked 1 out of 24)

2007, Outstanding Contribution to Cardiovascular Research, Life Science Association of Manitoba

2006, Best Poster Presentation Award, International Symposium on Emerging Trends in Biochemistry, Chandigarh, India

2006, Travel Award, CSIR, 13th International Symposium on Atherosclerosis, Kyoto, Japan

2006, Best Poster Presentation Award, 13th International Symposium on Atherosclerosis, Kyoto, Japan

2005, Graduate Student Fellowship, ICMR, India

2003, Best Poster Presentation Award, National Symposium on Oxidative Stress, India

Student Awards

Niketa Sareen

  • Travel Award (SIRC, Italy) 2023
  • 3rd Place Winner& People’s Choice Award (3 MP) 2023
  • Honorable Mention in Poster Presentation (MSHRF, 2023) 2023
  • Arnold Naimark Young Investigator Award 2022
  • Major Award for Excellence in Cardiovascular Research (St. Boniface Hospital Foundation) 2021
  • Edwin Kroeger Award for Excellence in Cellular Physiology 2018
  • Second Award in Poster Presentation (Dr. Naranjan Dhalla Cardiovascular Awards Day) 2017
  • Pawan K. Singal Graduate Scholarship in Cardiovascular Sciences 2017-2018
  • Research Manitoba 2017 – 2019
  • University of Manitoba Graduate Fellowship (Declined to accept Research Manitoba) 2017
  • FGS Travel Award (University of Manitoba) 2016
  • UMGSA Travel Award (University of Manitoba) 2016
  • IGS Scholarship (University of Manitoba) 2016 – 2017
  • CIHR IMPACT Doctoral Award (University of Manitoba) 2016
  • IGS Scholarship (University of Manitoba) 2016
  • Institute of Cardiovascular Sciences Studentship (University of Manitoba) 2015
  • IGSES (University of Manitoba) 2014

Abhay Srivastava

  • First place in oral presentation at ‘5MReSparks’ Post-Graduate Research Competition at the Global Talents in Science Symposium 2023
  • First place in ICS Poster Day Oral presentation competition at ICS, St. Boniface Hospital Research, Winnipeg, MB
  • Martin Morad Young Investigator Exchange Award at the International Academy of Cardiovascular Sciences at IACS-ES, 2023
  • Second place in 3 minute Post-doctoral competition at University of Manitoba
  • Dean of the Rady Faculty of Health Sciences Post-Doctoral Fellow Award for excellence
  • Honorary mention, poster competition at CHRD 2022
  • Canadian Institutes of Health Research (CIHR) Post-Doctoral Fellowship with percent rank being 7.88% within the committee
  • Arnold Naimark Young Investigator Award
  • Second prize for oral presentation at 22nd Annual 2020 ICS Naranjan Dhalla Awards Poster Day Competition

Keshav Narayan Alagarsamy

  • Grant Pierce Award for Excellence in Cardiovascular Physiology
  • Graduate Student Merit Award (GSMA) – HSGSA
  • ED KROEGER TRAVEL AWARD
  • Bioscience Association Manitoba (BAM) Poster Award – MSHRF
  • Faculty of Graduate Studies Research Completion Scholarship
  • Archie McNicol Prize for first place, 3MT 2023
  • Gary Lopaschuk Graduate Student Award, 10th Annual Meeting of the North American Section of the International Academy of Cardiovascular Sciences, held in Tampa, Florida (September 7-9, 2023)

Leena Regi Saleth

  • Gary Lopaschuk Graduate Student Award, 10th Annual Meeting of the North American Section of the International Academy of Cardiovascular Sciences, held in Tampa, Florida (September 7-9, 2023)

Canadian Institute of Health Research (CIHR)

Heart and Stroke Foundation of Canada- Grant-in-Aid

Canadian Foundation for Innovation (CFI)

Horizon Europe-MSCA-2021-SE-01 (EU)

Canadian Institute of Health Research (CIHR)

Natural Science and Engineering Council of Canada (NSERC)

Canadian Institute of Health Research (CIHR)

Canadian Institute of Health Research (CIHR)

CANUSA St. Boniface-Mayo Clinic, Science Without Border Program

Research Manitoba

2017-2018          St. Boniface Hospital Foundation/Wawanesa Insurance, to purchase MEA system

2015-2016          Thorlakson Foundation

2014-2015          Manitoba Medical Service Foundation

2013-2016          St. Boniface Hospital Foundation/Sons and Daughters of Italy, to set up Canada Italy Tissue Engineering Laboratory

Canada Italy Tissue Engineering Laboratory (CITEL)

CITEL is a translational research program which was established in 2013 by Dr. Grant Pierce at the St. Boniface Albrechtsen Research Centre. This is a unique collaboration with the University of Rome and Scuola Superiore in Pisa Italy. The Principal Investigators directing this program are Dr. Sanjiv Dhingra (St. Boniface Research Centre), Dr. Paolo Di Nardo (University of Rome) and Dr. Vincenzo Lionetti  (Pisa, Italy). CITEL is committed to synthesis and application of novel stem cells and biomaterials based therapies for cardiac regeneration and repair. CITEL is also promoting exchange of students/postdocs/clinical fellows between St. Boniface Hospital Research Centre and University of Rome. In the past 5 years, two master’s students, Mr. Matteo Ciocci (in March 2015) and Ms. Sara Loconsolo (in March 2016) from the University of Rome, visited Dr. Sanjiv Dhingra’s laboratory at the Institute of Cardiovascular Sciences, St. Boniface Albrechtsen Research Centre. Under the banner of CITEL program, Dr. Dhingra and Dr. Di Nardo organized an international conference on the Future of Regenerative Medicine in Tuscania, Italy in October 2017. This meeting was attended by more than 70 scientists, clinicians and industry personnel to discuss clinically relevant issues related to regenerative medicine and tissue engineering. Through these collaborative efforts Dr. Di Nardo and Dr. Dhingra also edited a book entitled “Adult Stem Cells” published by Springer in the series “Methods in Molecular Biology”.

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