EP-147: A dult-Derived Mesenchymal Stem Cells and Stromal Vascular Fraction from Adipose Tissue as a Therapeutic Treatment for Osteoarthritis H. Mahmood, N. Smith, J. Feller, M. Berman, E. Lander, J. Braslow, J. See, K. Abeyratne, C. Hancock

Disclosure Statement This presentation does not depict any activity regarding financial interest or other relationships (i.e., grants, research support, consultant, speakers bureau, major stock holder, etc) with the manufacturer(s) of any commercial product(s), (drugs, devices, or services) and with any commercial supporters of the activity.

Stem Cell Potency – Totipotent – Pluripotent – Multipotent – Oligopotent – Unipotent Types – Embryonic – Adult Tissue – Autograft – Allograft – Xenograft Background

1908 The term “stem cell” was proposed by the histologist Alexander Maksimov 1978 Haematopoietic stem cells are discovered in human cord blood 1981 "Embryonic Stem Cell“ described in mice 1992 Neural stem cells are cultured in-vitro as neurospheres 2003 Adult stem cells found in children’s primary teeth 2005 UC Irvine partially restores the ability of rats with paralyzed spines to walk through the injection of human neural stem cells History of Stem Cells Harper, Alicia. "Stem Cell Therapy." Global Hydranencephaly Foundation Global Hydranencephaly Foundation, n.d. Web. 21 Apr

Stem Cells – A History October 2006: Scientists in England create the first ever artificial liver cells using umbilical cord blood stem cells. March 2008: Cartilage regeneration in the human knee using autologous adult mesenchymal stem cells. 30 October 2008: Embryonic-like stem cells from a single human hair. January 2009: Reversal of autoimmune-caused type 1 diabetes by Cord Blood Derived Multipotent Stem Cells in an animal experiment. 2011: Stem cells from endangered species, a breakthrough that could save animals in danger of extinction. 2013: First time mice adult cells were reprogrammed into stem cells in vivo. 2013: 3D printer that can produce clusters of living human ESCs,.

Disk Regeneration 15 Guinea Pigs Disk Lanced Levels Randomized Spine (Phila Pa 1976) Mar 15;36(6):E Autologous stem cell therapy maintains vertebral blood flow and contrast diffusion through the endplate in experimental intervertebral disc degeneration. Bendtsen M 1, Bünger CE, Zou X, Foldager C, Jørgensen HS

T2 Mapping

JBJS January Patients Partial medial menisectomy Three Groups - Randomized – 50 Million Stem Cells – 150 Million Stem Cells – Control – Hyaluronate (Hyaluronic Acid/ hyaluronan) C. Thomas Vangsness, Jr. MD. Et al. Adult Human Mesenchymal Stem Cells (MSC) Delivered via IntraArticular Injection to the Knee, Following Partial Medial Menisectomy, Journal of Bone and Joint Surgery, January 2014

JBJS 2014 Stem Cell - Conclusions No Abnormal (ectopic) tissue formation No Clinically Important Safety Issues Identified Significant Increase in Meniscal Volume in Test group and none in Control group Osteoarthritis patients – Reduction in Pain in Test group and none in Control group AAOS - “Stem Cell Therapy Following Meniscus Knee Surgery May Reduce Pain, Restore Meniscus”

Patient Safety – First Concern IRB Approved Study Patient - Study Enrollment Determine Target Site Suppress Fat Signal Osseous Edema Capsulitis Pericapsulitis

T2 Prolongation Suppress Fat Signal Osseous Edema Capsulitis Pericapsulitis STIR or T2 FS—Inflamed Facets

T1 Post Contrast FS—Inflamed Facets

Stromal Vascular Fraction (SVF) – Stem Cell Concentrate: Preadipocytes Mesenchymal Stem cells (MSCs) Endothelial Progenitor cells T cells, B cells, Mast cells Adipose tissue macrophages

Benefits of Image Guidance to Perform Therapeutic Stem Cell Injections: Accurate targeting of pain generator Accurate delivery to target Objective evidence of response to therapy CT Guidance: 80% Improvement Fluoroscopy: 50% Improvement Blind Injection: 30% Improvement ASSR Spine Injection Background

Materials: CT Image Guidance

Cervicalgia – Facet Joint Pain Determine Inflamed Facet Joint/s T2 Fat Sat, STIR, or T1 Fat Sat Post contrast

Cervicalgia

Facet Arthropathy

Facet Joint Injections

Stem Cell & SVF Facet Joint Injections 29 Patients

Stromal Vascular Fraction & Stem Cell Injection Facet Joint Analysis

Stromal Vascular Fraction & Stem Cell Injection Facet Joint Analysis

Pain Score Averages

SFV & Stem Cell Injection Therapy

Summary Conclusion: Image Guidance SVF & Stem Cell Therapy I.Determine Target. II.Delivery of Stem cells & SVF to the target. III.Follow up response to therapy. IV.Positive Therapeutic Experience Observed V.Propose further Research Thank you!

Christopher Hancock, MD Hibah Mahmood