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Regenerative Medicine
Today and Tomorrow
Curtis L. Beauregard, MD, MS Neurological Surgery, The Wellness Group
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
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
Ultimate Goals of Regenerative Medicine?
Source: NIH, “Summary of the President’s FY 2004 Budget,” February 3, 2003
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
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
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
Where are Stem Cell Therapy Clinical Trials Being Performed?
What Clinical Applications are Stem Cells Being Evaluated For?
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
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.
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
Outcomes of Stem Cell Treatments for Orthopedic Indications
Orthopedic Outcomes
Orthopedic Outcomes
Orthopedic Outcomes
Orthopedic Outcomes
Orthopedic OutcomesOsteoarthritis of the Knee – Rx with Autologous BM
Regenexx Patient Registry Data 2008-2015
Orthopedic OutcomesOsteoarthritis of the Knee – Rx with Autologous BM
Regenexx Patient Registry Data 2008-2015
Orthopedic OutcomesOsteoarthritis of the Hip – Rx with Autologous BM
Current Stem Cell Therapy OutcomesOsteoarthritis of the Hip – Rx with Autologous BM
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
Examples of Stem Cell Therapy Potential
Heart Disease – Acute MI Treatment Scarring and atrophy following AMI can lead to heart failure and fatal arrhythmias
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
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
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.
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.:
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
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
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..
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.
Examples of Stem Cell Therapy Potential for CNS Injury
Examples of Stem Cell Therapy Potential for CNS Injury
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.
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.
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.
Other Examples of Stem Cell Therapy Potential
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.
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.
Examples of Stem Cell Applications
http://www.youtube.com/watch?feature=player_embedded&v=eXO_ApjKPaI
Other Examples of Stem Cell Therapy Potential: Most Important!
Potential Impact of Stem Cell Therapies
Potential Impact of Stem Cell Therapies
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.
The Future
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)
Stem Cell Targeting• Burnham Peptides – developed at Stanford, unique
molecules demonstrated to “home-in” on specific body tissues
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:
“Engineered” Blood
“Engineered” Blood
Regenerative Medicine IS The Future of Medicine Now!
Thank You
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