San Diego Regenerative Medicine Institute
Human Stem Cells --- Key to Regeneration
San Diego Regenerative Medicine Institute (SDRMI), a nonprofit independent biomedical research institute with 501C3 IRS tax-exempt status, was established in 2010 with funding from National Institutes of Health (NIH) -- (Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH R21HD056530, PI, Parsons; National Institute on Aging, NIH K01AG024496, PI, Parsons) -- committing to the leading position in human pluripotent stem cell (hPSC)-based regenerative medicine to provide the next generation of cell-based therapeutic solutions for unmet medical challenges in world-wide major health problems.
SDRMI is a stem cell focused research organization founded to leverage stem cell treatment development and manufacturing innovations for unmet medical needs. The inception of SDRMI is driven by the urgent need for clinical translation of hPSC research discoveries and technologies to provide stem cell treatments for major human diseases challenging traditional medicine.
SDRMI has built proprietary groundbreaking PluriXcel human stem cell technology enabling large-scale production of high quality clinical-grade hPSC lines and direct conversion of such nonfunctional pluripotent cells by small molecule induction into large commercial scales of high quality functional human neuronal or cardiomyocyte derivatives, which not only constitutes clinically representative progress in both human neuronal and cardiac therapeutic products for treating a wide range of incurable or hitherto untreatable neurological and heart diseases, but also offer manufacturing innovations for production scale-up and creation of replacement tissue and organ products. Medical innovations of PluriXcel technology provide scalable platforms to ensure a high degree of efficacy and safety of hPSC-derived cellular products, thus robust clinical benefits leading to therapies, for treating major human diseases challenging traditional medicine, which represent the next generation of human cell therapy products, offering purity, large-scale production, high quality, safety, and effectiveness for commercial and therapeutic uses over all other existing human cell sources. Manufacturing innovations of PluriXcel technology provide scale-up cGMP manufacturing capability or techniques for production of large quantities of high quality clinical-grade hPSC-based cell therapy products to support clinical trials and tissue or organ engineering, improving the availability, reproducibility, accessibility, and standardization of manufacturing materials, technologies, and processes to create human repairing or replacing cell, tissue, and organ products. PluriXcel technology platforms pave the way for further development of cutting-edge automated high-content systems for systematic functional assembly of the in vitro tissues and organs from hPSC in a 3D setting that reflect the biological complexity and microenvironment niche of the in vivo human organ system, enabling automated high content and high-throughput analysis of CNS or heart circuitry and dynamics, and systems developmental biology models of the complex human embryonic development. Xcel prototypes of PluriXcel technology-based cell therapy products offer currently the only available human cell sources with adequate regenerative capacity for CNS and myocardium repair in the clinical setting, and for creating human CNS- and heart-related tissue or organ products, will facilitate CNS and myocardial tissue-engineering and accelerate development of safe and effective cell therapies for a wide range of incurable or hitherto untreatable neurological and heart diseases challenging traditional medicine.
Pluripotent human embryonic stem cells (hESC), the nature source of hPSC, hold great potential for cell replacement and regeneration therapies for human diseases that have been challenging for traditional medicine, such as neurodegenerative diseases and heart diseases. The genetically stable hESCs proffer a pluripotent reservoir for in vitro derivation of a large supply of disease-targeted human somatic cells that are restricted to the lineage in need of repair. The translational values of discoveries and innovations in hESC research have transformative therapeutic utility to extend healthy life and reduce the burdens of illness. To address the unmet medical needs, SDRMI is committed to develop groundbreaking hESC technology platforms and innovative cell-based regenerative medicine approaches targeting world-wide major health problems.
Pluripotent hESC have both the unconstrained capacity for long-term stable undifferentiated growth in culture and the intrinsic potential for differentiation into all somatic cell types in the human body, holding tremendous potential for restoring human tissue and organ function. Derivation of hESCs, essentially the in vitro representation of the pluripotent inner cell mass (ICM) or epiblast of the human blastocyst, provides not only a powerful in vitro model system for understanding human embryonic development, but also an unlimited source for in vitro derivation of a large supply of disease-targeted human somatic cells for tissue engineering and cell therapy. There is a large unmet healthcare need to develop hESC-based therapeutic solutions to provide optimal regeneration and reconstruction treatment options for normal tissue and function restoration in many devastating and life-threatening diseases and injuries. The hESC and their cell therapy derivatives are considerably less immunogenic than adult tissues. It is also possible to bank large numbers of human leukocyte antigen isotyped hESC lines so as to improve the likelihood of a close match. The pluripotent hESC itself cannot be used for therapeutic applications. It has been recognized that non-functional pluripotent hESC must be transformed into fate-restricted functional derivatives before use for cell therapy. However, realizing the developmental and therapeutic potential of hESC derivatives has been hindered by conventional approaches for generating functional cells from pluripotent cells through uncontrollable, incomplete, and inefficient multi-lineage differentiation. Conventional approaches rely on multi-lineage inclination of pluripotent cells through spontaneous germ layer differentiation, which yields embryoid body (EB) consisting of a mixed population of cell types that may reside in three embryonic germ layers and results in inefficient, incomplete, and uncontrollable differentiation that is often followed by phenotypic heterogeneity and instability, hence, a high risk of tumorigenicity. Growing evidences indicate that incomplete lineage specification of pluripotent cells via multi-lineage differentiation often result in poor performance of such stem cell derivatives and tissue-engineering constructs following transplantation. In order to generate a large supply of uniform functional cells for tissue engineering and cell therapy, how to channel the wide differentiation potential of pluripotent hESC efficiently and predictably to a desired lineage has been a major challenge for clinical translation. In addition, most currently available hESC lines were derived and maintained on animal feeder cells and proteins, therefore, such hESC have been contaminated with animal biologics and unsuitable for clinical application. Without a practical strategy to convert pluripotent cells direct into a specific lineage, previous studies and profiling of hESC differentiating multi-lineage aggregates have compromised their implications to molecular controls in human embryonic development.
SDRMI has developed novel strategies – PluriXcel technology platforms -- for well-controlled efficiently directing pluripotent hESC exclusively and uniformly towards clinically-relevant cell types in a lineage-specific manner, which is not only crucial for unveiling the molecular and cellular cues that direct human embryogenesis, but also vital to harnessing the power of hESC biology for cell-based regenerative medicine. SDRMI milestone advances and medical innovations in hESC research transform non-functional pluripotent hESCs into fate-restricted functional cell therapy derivatives, which dramatically increases the clinical efficacy of graft-dependent repair and safety of hESC-derived cellular products. SDRMI technology breakthroughs enable high efficient direct conversion of hPSC into a large supply of clinical-grade high purity neuronal cells or heart muscle cells for developing safe and effective stem cell therapies as treatments or cures for a wide range of neurological and cardiovascular diseases, bringing cell-based regenerative medicine to a turning point. Currently, the Xcel prototypes of hESC neuronal and cardiomyocyte cell therapy derivatives are the only available human cell sources with adequate cellular pharmacologic utility and capacity to regenerate CNS (central nervous system) neurons and contractile heart muscles, vital for CNS and heart repair in the clinical setting.
US patent# 8,716,017, issued 2014 by USPTO, “Technologies, Methods, & Products of Small Molecule-Directed Tissue & Organ Regeneration from Human Pluripotent Stem Cells”, PCT/US 20120301437, US 20160115446, WO/2012/078470. Inventor: Xuejun H Parsons; Press Release: Xcelthera Inc secures first U.S. patent for large-scale production of high quality human embryonic stem cells and their neuronal and heart muscle cell therapy products.
US patent# 9,428,731, issued 2016 by USPTO, “Technologies, Methods, & Products of Small Molecule-Directed Tissue & Organ Regeneration from Human Pluripotent Stem Cells”, PCT/US 20120301437, US 20140193380, WO/2012/078470. Inventor: Xuejun H Parsons.
“Defined Media for Pluripotent Stem Cells”, PCT/US 20050233446, 20070010011, 20080241919, WO2005/065354. Primary Inventor: Xuejun H Parsons.
1. Parsons XH. Direct conversion of pluripotent human embryonic stem cells (human ES cells) under defined culture conditions into human neuronal or cardiomyocytes cell therapy derivatives. Methods Mol. Biol. 2016;1307:299-318. Chapter on Human Embryonic Stem Cells: Methods and Protocols, 2nd Edition. Springer’s Protocols. doi: 10.1007/7651_2014_69. PMID: 24500898.
2. Parsons XH. Human pluripotent stem cell-based PluriXcel technology platforms provide stem cell treatment development and manufacturing innovations for progressing to the clinic. J. Regen. Ther. 2106, 1:1-8.
3. Parsons XH. PluriXcel technology platforms as paradigm for heart assembly from pluripotent human embryonic stem cell cardiomyocyte derivatives. J. Clinic. Exp. Cardiology 2016 (in press).
4. Parsons XH. Directing pluripotent human embryonic stem cells towards lineage-specific cell therapy derivatives for regenerative medicine. Chapter covering human embryonic stem cells, Gene and Cell Therapy: Therapeutic Mechanisms and Strategies, 4th Edition, edited by Nancy Smyth Templeton, CRC Press, 2015; Chapter 31:795-818, Taylor and Francis, Print ISBN: 978-1-4665-7199-0, eBook ISBN: 978-1-4665-7200-3.
5. Parsons XH. Constraining the pluripotent fate of human embryonic stem cellsfor tissue engineering and cell therapy – the turning point of cell-based regenerative medicine. British Biotech. J. 2013;3(4):424-457. doi: PMID: 24926434. PMCID: 4051304.
6. Parsons XH. . Embedding the future of regenerative medicine into the open epigenomic landscape of pluripotent human embryonic stem cells. Ann. Rev. Res. Biol. 2013;3(4):323-349. PMID: 25309947. PMCID: 4190676.
7.Parsons XH. Current state of regenerative medicine: moving stem cell research from animals into humans for clinical trials (Critical Review). JSM Regen Med Bio Eng 2014;1(1):1005.
8. Parsons XH. The openness of pluripotent epigenome – defining the genomic integrity of stemness for regenerative medicine (Editorial). Int. J. Cancer Ther. Oncol. 2014;2(1):020114. doi: 10.14319/ijcto.0201.14.
9. Parsons XH. The designation of human cardiac stem cell therapy products for human trials (Editorial). J. Clin. Trial Cardiol. 2014;1(1):02. JCTCD-13-Ed-107. doi: 10.15226/2374-6882/1/1/00102.
10. Parsons XH. Human stem cell derivatives retain more open epigenomic landscape when derived from pluripotent cells than from tissues. J. Regen. Med. 2013;1:2. doi: 10.4172/2325-9620.1000103. PMID: 23936871. PMCID: 3736349.
11. Parsons XH, Parsons JF, Moore DA. Genome-scale mapping of microRNA signatures in human embryonic stem cell neurogenesis. Mol. Med. Ther. 2013;1:2. doi: 10.4172/2324-8769.1000105. PMID: 23543894. PMCID: 3609664.
12. Parsons XH. Reviving cell-based regenerative medicine for heart reconstitution with efficiency in deriving cardiac elements from pluripotent human embryonic stem cells (Editorial). Cardiol. Pharmacol. 2013;2(3):e112. doi: 10.4172/2329-6607.1000e112.
13. Parsons XH. Exploring future cardiovascular medicine: heart precursors directed from human embryonic stem cells for myocardium regeneration (Editorial). Cardiol. Pharmacol. 2013;2(3):e110. doi: 10.4172/2329-6607.1000e110.
14. Parsons XH. Cellular medicine for the heart - the pharmacologic utility and capacity of human cardiac stem cells (Editorial). J. Clinic. Exp. Cardiology 2013;S11-e001. doi: 10.4172/2155-9880.S11-e001.
15. Parsons XH. An engraftable human embryonic stem cell neuronal lineage-specific derivative retains embryonic chromatin plasticity for scale-up CNS regeneration. J. Reg. Med. & Tissue Eng. 2012;1:3. doi: 10.7243/2050-1218-1-3. PMID: 23542901. PMCID: 3609668.
16. Parsons XH. MicroRNA profiling reveals distinct mechanisms governing cardiac and neural lineage-specification of pluripotent human embryonic stem cells. J. Stem Cell Res. Ther. 2012;2:124. doi: 10.4172/2157-7633.1000124. PMID: 23355957. PMCID: 3554249.
17. Parsons XH. Mending the broken heart - Towards clinical application of human embryonic stem cell therapy derivatives (Editorial). J. Clinic. Exp. Cardiology 2012;3(12):e116. doi: 10.4172/2155-9880.1000e116.
18. Parsons JF, Smotrich DB, Gonzalez R, Snyder EY, Moore DA, Parsons XH. Defining conditions for sustaining epiblast pluripotence enables direct induction of clinically-suitable human myocardial grafts from biologics-free human embryonic stem cells. J. Clinic. Exp. Cardiology 2012;S9-001. doi: 10.4172/2155-9880.S9-001. (Special Issue on Heart Transplantation). PMID: 22905333. PMCID: 3419496.
19. Parsons XH. The dynamics of global chromatin remodeling are pivotal for tracking the normal pluripotency of human embryonic stem cells. Anatom. Physiol. 2012;S3:002. doi: 10.4172/2161-0940.S3-002. (Special Issue on Stem Cell Biology). PMID: 23543848. PMCID: 3609651.
20. Parsons XH, Teng YD, Parsons JF, Snyder EY, Smotrich DB, Moore DA. Efficient derivation of human cardiac precursors and cardiomyocytes from pluripotent human embryonic stem cells with small molecule induction. J. Vis. Exp. 2011;57:e3274. doi: 10.3791/3274. PMID: 22083019. PMCID: 3308594.
21. Parsons XH, Teng YD, Parsons JF, Snyder EY, Smotrich DB, Moore DA. Efficient derivation of human neuronal progenitors and neurons from pluripotent human embryonic stem cells with small molecule induction. J. Vis. Exp. 2011;56:e3273. doi: 10.3791/3273. PMID: 22064669. PMCID: 3227216.
22. Parsons XH, Teng YD, Moore DA, Snyder EY. Patents on technologies of human tissue and organ regeneration from pluripotent human embryonic stem cells. Recent Patents on Regenerative Medicine 2011;1:142-163. PMID: 2335596. PMCID: 3554241.
23. Parsons XH. “Small molecule lineage-specification direct from the pluripotent state of human embryonic stem cells” & “A human embryonic neuronal progenitor induced direct from the pluripotent state of human embryonic stem cells for scale-up CNS regeneration” (posters), published on Faculty-1000 at http://f1000.com/posters/browse/summary/ 1089478 & http://f1000.com/posters/browse/summary/1089479, 2011 World Stem Cell Summit, Pasadena, CA.
24. Parsons XH, Teng YD, Snyder EY. Important precautions when deriving patient-specific neural elements from pluripotent cells. Cytotherapy 2009;11:815-824. doi: 10.3109/14653240903180092. PMID: 19903095. PMCID: 3449142.
Xuejun H. Parsons, PhD,
Chairman of the Board/CEO/President
board of directors and scientific advisory board
Dr. Xuejun H Parsons received her PhD in Biochemistry, Molecular, and Cell Biology from Cornell University in 1998, and completed her PostDoc studies as a Leukemia and Lymphoma Society Research Fellow at University of California at San Diego in 2002. She has a broad background in biomedical research and life sciences industry, with a great deal of expertise and leadership in the emerging technology of human pluripotent stem cell (hPSC) based regenerative medicine, in-depth understanding of hPSC research to the advance of medicine and improvement of human health, and entrepreneurship. Following her postdoc training in the field of molecular biology, she was awarded a NIH mentored research scientist career development award (NIH K01AG024496, titled “Epigenetic Controls in hESC Dopaminergic Fate”) in 2005 for successful transition of her career into the human stem cell field as PI. From 2005-2008, she also served as the key personnel and project leader in one of the NIH exploratory centers for pluripotent human embryonic stem cell (hESC) research, and have led the collaborative effort to develop the utility of hESC as a model system for a diverse range of biological and medical problems with her original research and ability to integrate diverse sources of information to develop novel approaches. She is the Co-Founder/CEO of San Diego Regenerative Medicine Institute, Xcelthera INC, and PluriStem Biopharmaceutical Ltd. Previously; she was a stem cell scientist and/or faculty at University of California and Sanford Burnham Prebys Medical Discovery Institute. Her original hPSC research breakthroughs render well-controlled high efficient neuronal or cardiac lineage-specific conversion directly from the pluripotent state of hPSC by small molecule induction, which opens the door for human neural and cardiac tissue/organ engineering and regeneration as well as to investigate molecular neurogenesis and cardiogenesis in human embryonic development using powerful in vitro model systems. She is the first to develop the proprietary breakthrough PluriXcel human stem cell technology for large-scale production of high quality clinical-grade pluripotent hPSC lines and their functional human neuronal and cardiomyocyte cell therapy derivatives for commercial and therapeutic uses, which has overcome some major obstacles in bringing hPSC therapy derivatives towards clinical applications for unmet medical challenges in incurable or hitherto untreatable neurological/neurodegenerative and cardiovascular/heart diseases, and which has generated intellectual property to enable therapeutic development, commercialization, and clinical practice of proprietary hPSC therapy tools and products for startups. Her medical and manufacturing innovations provide life scientists and clinicians with novel, efficient, and powerful resources and tools to address major health concerns, which will shape the future of medicine by providing hPSC-based technology for human tissue and function restoration, and bringing new therapeutics into the market.