curtis l. beauregard, md, ms neurological surgery, the ... · regenerative medicine today and...
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Regenerative Medicine
Today and Tomorrow
Curtis L. Beauregard, MD, MS Neurological Surgery, The Wellness Group
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What is Regenerative Medicine?
• Primary Aims: – 1. Facilitate and maximize the body’s
natural ability to heal itself from injury or disease
• Metabolic optimization through diet, exercise, hormone replacement, and nutritional supplementation
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What is Regenerative Medicine– 2. Creating functional cells and tissues to repair
or replace damaged or diseased tissue when the healing capacity of the body is inadequate
• Use of exogenous “growth factors”, other medications to further stimulate innate repair mechanism.
• Cell and tissue replacement therapy- aka “stem cell therapy”
• Retard or reverse the effects of aging
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Ultimate Goals of Regenerative Medicine?
Source: NIH, “Summary of the President’s FY 2004 Budget,” February 3, 2003
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Stem Cells: The Main Event
• Although regenerative medicine encompasses multiple areas, stem cell treatments are undoubtedly the area of greatest interest and promise
• Stem cells of all types– embryonic, fetal, adult, and induced pluipotent– are already being widely studied for clinical applications
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Stem Cell Applications
• Basic Science: – Although not as “newsworthy” as direct clinical
applications, stem cells have numerous, potentially groundbreaking uses in basic research:
• May assist with clarification of complex events, such as:
– Molecular mechanisms for gene control – Role of signals in gene expression and differentiation of cell types – Genetic and molecular models of carcinogenesis
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Stem Cell Applications
• Basic Science: • Biotechnology (Drug Discovery and
Development) – Safety testing of new drugs on differentiated and
undifferentiated human cell lines – An invaluable tool for rapid screening of potential new
drugs that avoids many of the pitfalls of animal testing
Source: “Pluripotent stem cells in disease modelling and drug discovery.” Nature Reviews Molecular Cell Biology 17, 170–182 (2016) doi:10.1038/nrm.2015.27 Published online 28 January 2016
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Where are Stem Cell Therapy Clinical Trials Being Performed?
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What Clinical Applications are Stem Cells Being Evaluated For?
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What Clinical Applications are Stem Cells Currently Being Used For?
• Orthopedic Conditions – by far the most common current clinical applications – Osteoarthritis
• Knee, Shoulder, and Hip joint are most commonly treated
• Spinal disease and smaller joints also being treated, though not as commonly (yet) and less outcome data available
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What Clinical Applications are Stem Cells Currently Being Used For?
• Orthopedic Conditions – Osteoarthritis
• Various protocols in use, predominantly autologous MSCs harvested either from adipose or bone marrow, but some centers using allogenic, umbilical/amniotic tissues
• Large case series with extended follow-up support MSC treatment of OA as safe and effective, with very low risk of serious adverse events.
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What Clinical Applications are Stem Cells Currently Being Used For?
• Orthopedic Conditions
– Other Ortho applications include complete ligament and cartilage tears
• Particular promise shown in treating ACL/MCL and meniscal complete tears
Source: Andreas Schmitt, Martijn van Griensven, Andreas B. Imhoff, and Stefan Buchmann, “Application of Stem Cells in Orthopedics,” Stem Cells International, vol. 2012, Article ID 394962, 11 pages, 2012. doi:10.1155/2012/394962
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Outcomes of Stem Cell Treatments for Orthopedic Indications
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Orthopedic Outcomes
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Orthopedic Outcomes
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Orthopedic Outcomes
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Orthopedic Outcomes
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Orthopedic OutcomesOsteoarthritis of the Knee – Rx with Autologous BM
Regenexx Patient Registry Data 2008-2015
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Orthopedic OutcomesOsteoarthritis of the Knee – Rx with Autologous BM
Regenexx Patient Registry Data 2008-2015
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Orthopedic OutcomesOsteoarthritis of the Hip – Rx with Autologous BM
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Current Stem Cell Therapy OutcomesOsteoarthritis of the Hip – Rx with Autologous BM
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What Clinical Applications are Stem Cells Currently Being Used For?
• Cardiac Conditions – Both IV and direct intracardiac injection
protocols are being evaluated for treatment of multiple cardiac conditions:
• Post AMI to reduce scarring and non-functional myocardium
• CHF/cardiomyopathies with very low EF • Future promise for 3D tissue engineering of
complex structures such as complete valves
Source: Clinical Applications of Stem Cells for the Heart.” https://doi.org/10.1161/01.RES.0000155333.69009.63 Circulation Research. 2005;96:151-163
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Examples of Stem Cell Therapy Potential
Heart Disease – Acute MI Treatment Scarring and atrophy following AMI can lead to heart failure and fatal arrhythmias
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Examples of Stem Cell Therapy PotentialAnimal Studies using MSCs given 8 hours following induced ischemia .
Source: Krishna K.A. et al. Myocardial infarction and stem cells. Journal of Pharmacy and Bioallied Sciences. 2011;3(2):182-188. doi:10.4103/0975-7406.80761
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Examples of Stem Cell Therapy Potential
Human Phase I study of human allogenic MSCs given IV after AMI: J Am Coll Cardiol. 2009 Dec 8;54(24):2277-86. doi: 10.1016/j.jacc.2009.06.055
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What Clinical Applications are Stem Cells Currently Being Used For?
• Pulmonary Conditions – Since IV administration results in primary
deposition of cells in the pulmonary vasculatures, IV treatment is particularly promising for pulmonary diseases:
• Asthma • COPD • Cystic Fibrosis
Source: Weiss DJ. Current Status of Stem Cells and Regenerative Medicine in Lung Biology and Diseases. Stem cells (Dayton, Ohio). 2014;32(1):16-25. doi:10.1002/stem.1506.
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What Clinical Applications are Stem Cells Currently Being Used For?
• Neurological Conditions – Multiple Sclerosis
• Initial studies show promise, with many patients seeing either improvement in deficits or prevention of disease progression
• Unclear what best route/cell source/”dosage” is most effective at present
SourceMeamar R, Nematollahi S, Dehghani L, et al. The role of stem cell therapy in multiple sclerosis: An overview of the current status of the clinical studies. Advanced Biomedical Research. 2016;5:46. doi:10.4103/2277-9175.178791.:
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What Clinical Applications are Stem Cells Currently Being Used For?
• Neurological Conditions – Stroke:
• Multiple studies ongoing with varied treatment protocols
• Recent small (18 patients) study at Stanford showed “miraculous” results from direct brain implantation of allogenic “modified” MSCs
• All patients >1 year post stroke • Numerous patients had amazing motor recovery–
from non-ambulatory to ambulatory, non-functional limbs to 4/5 motor strength
Source: http://stroke.ahajournals.org/content/early/2016/06/02/STROKEAHA.116.012995
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What Clinical Applications are Stem Cells Currently Being Used For?
• Neurological Conditions – Stroke:
• Multiple studies ongoing with varied treatment protocols
• Recent small (18 patients) study at Stanford showed “miraculous” results from direct brain implantation of allogenic “modified” MSCs
• All patients >1 year post stroke • Numerous patients had amazing motor recovery–
from non-ambulatory to ambulatory, non-functional limbs to 4/5 motor strength
http://stroke.ahajournals.org/content/early/2016/06/02/STROKEAHA.116.012995
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What Clinical Applications are Stem Cells Currently Being Used For?
• Neurological Conditions • Spinal Cord Injury • Parkinson’s and Alzheimer’s Disease
– As with other systemic neurological diseases, the issue of best delivery method, cell type, and “dosage” are important elements that require additional research
– Cell culture/amplification likely to be important for these applications
Sources:Tewarie RSN, Hurtado A, Bartels RH, Grotenhuis A, Oudega M. Stem Cell–Based Therapies for Spinal Cord Injury. The Journal of Spinal Cord Medicine. 2009;32(2):105-114. Björklund LM. Stem cell therapy for Parkinson’s disease. Dialogues in Clinical Neuroscience. 2004;6(3):303-311 Tong LM, Fong H, Huang Y. Stem cell therapy for Alzheimer’s disease and related disorders: current status and future perspectives. Experimental & Molecular Medicine. 2015;47(3):e151-. doi:10.1038/emm.2014.124..
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Examples of Stem Cell Therapy Potential for CNS Injury
Source: V.I. Seledtsov, S.S. Rabinovich, O.V. Parlyuk, et al, Biomedicine and Pharacotherapy. 59(2005) 415-420.
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Examples of Stem Cell Therapy Potential for CNS Injury
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Examples of Stem Cell Therapy Potential for CNS Injury
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What Clinical Applications are Stem Cells Currently Being Used For?
• Autoimmune Diseases – Lupus – Chron’s Disease – Rheumatoid Arthritis – Myasthenia Gravis
• The unique, immuno-modulatory and anti-inflammatory effects of MSCs may be of particular value in this group of diseases
Source: Hügle T, Daikeler T. Stem cell transplantation for autoimmune diseases. Haematologica. 2010;95(2):185-188. doi:10.3324/haematol.2009.017038.
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What Clinical Applications are Stem Cells Currently Being Used For?
• Ophthomology – Macular Degeneration – Retinitis Pigmentosa – Diabetic Retinopathy – Retinal Detachments
Source:Treatment Viability of Stem Cells in Ophthalmology VS Jeganathan et al. Curr Opin Ophthalmol 21 (3), 213-217. 5 2010.
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What Clinical Applications are Stem Cells Currently Being Used For?
• Urology – Interstitial Cystitis – Peyronie’s Disease – Erectile Dysfunction
Source:Kim JH, Song YS. Current status of stem cell therapy in urology. Korean Journal of Urology. 2015;56(6):409-411. doi:10.4111/kju.2015.56.6.409.
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Other Examples of Stem Cell Therapy Potential
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Other Examples of Stem Cell Therapy Potential
Source: “Mesenchymal stem cell therapy for nonhealing cutaneous wounds.” Plast Reconstr Surg. 2010 Feb;125(2):510-6.
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Other Examples of Stem Cell Therapy Potential
Source: Seo BF, Jung S-N. The Immunomodulatory Effects of Mesenchymal Stem Cells in Prevention or Treatment of Excessive Scars. Stem Cells International. 2016;2016:6937976. doi:10.1155/2016/6937976.
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Examples of Stem Cell Applications
http://www.youtube.com/watch?feature=player_embedded&v=eXO_ApjKPaI
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Other Examples of Stem Cell Therapy Potential: Most Important!
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Potential Impact of Stem Cell Therapies
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Potential Impact of Stem Cell Therapies
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Are Stem Cell Treatments Safe?
The risk of a stem cell therapy generally increases as the source changes. The safest cells are your own adult stem cells. Newer induced Pluripotent Stem Cells (iPSC), are artificial stem cells manufactured in a lab and as such are considered the most dangerous.
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The Future
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Stem Cell Targeting• Burnham Peptides – developed at Stanford, unique
molecules demonstrated to “home-in” on specific body tissues. Regenerative Medicine (May 2010, Vol. 5, No. 3, Pages 345-363)
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Stem Cell Targeting• Burnham Peptides – developed at Stanford, unique
molecules demonstrated to “home-in” on specific body tissues
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Tissue Engineering• In conjunction with advances in biomaterials and 3D printing
technology, stem cells may ultimately be used to produce complete tissues and organs for transplantation:
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“Engineered” Blood
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“Engineered” Blood
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Regenerative Medicine IS The Future of Medicine Now!
Thank You