Curtis L. Beauregard, MD, MS Neurological Surgery, The ... · Regenerative Medicine Today and...

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


• 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.


• 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 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


• 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


• 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.


• 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.:


• 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


• 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


• 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


• 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.


• 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.


• 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


Source: “Mesenchymal stem cell therapy for nonhealing cutaneous wounds.” Plast Reconstr Surg. 2010 Feb;125(2):510-6.


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

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

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

Regenerative Medicine IS The Future of Medicine Now!

Thank You

Curtis L. Beauregard, MD, MS Neurological Surgery, The ... · Regenerative Medicine Today and...

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