INSTITUTE OF REGENERATIVE AND MOLECULAR ORTHOPEDICS. DR. JOSEPH PURITA MD, FACS, FAAOS, FAAPM

Transcription

1 INSTITUTE OF REGENERATIVE AND MOLECULAR ORTHOPEDICS DR. JOSEPH PURITA MD, FACS, FAAOS, FAAPM

2 STEM CELL AND PLATELET RICH PLASMA INJECTIONS

3 The Revolution in Biologics Major Gap exists for treatment options between conservative treatment and surgery PRP and stem cells (BM-MNC s and fat ) offer an important therapeutic treatment option

4 The goal of the presentation is to allow the physician in an office setting to perform stem cell injections and platelet rich plasma in an efficient, safe and economical manner

5 PLATELET RICH PLASMA

6 PLATELET RICH PLASMA At one time it was thought that platelets were basically responsible for clotting the blood and that was all. Nothing could be further from the truth!! When the platelets are concentrated the growth factors are also concentrated. These growth factors are what cause things to heal.

7 A normal platelet count

8 Autologous platelet concentrate

9 PRP CONTENTS 1. Platelets 2. Neutrophil (PMN) % of circulating leukocytes 3. Monocyte macrophage % of circulating leukocytes. Highly motile and migrate to soft tissues 4. Fibroblast - produce collagen, reticular fibers, glycosaminoglycans, glycoprotein 5. Endothelial Cell - permeability barrier, regulate blood flow and vascular reactivity, vasodilators, vasoconstrictors, regulate inflammation and immunity 6. Keratinocyte - Stratified, squamous epithelial cells Primary function is to act as a barrier

10 Power of Platelets

11 GROWTH FACTORS Unfortunately, understanding the complex interactions involved with the various cytokines is made even more difficult because of the confusing nomenclature. Specifically, some cytokines are named for their cell of origin (e.g., platelet-derived growth factor [PDGF]), whereas others are named for their target cell (e.g., epidermal growth factor [EGF]). In addition, some cytokines are named for their first reported action (e.g., transforming growth factor-β). Finally, the actions of cytokines may be complex and numerous and unable to be described by a single name.

12 GROWTH FACTORS The mechanism of action of the cytokines may be through endocrine (secreted by one population of cells and having distant effects), autocrine (secreted by cells which then are themselves modulated by the factor), or paracrine (secreted by cells and affecting neighboring cell populations) activity

13 BOTTOM LINE FOR THE GROWTH FACTORS. THEY CAUSE STEM CELLS TO GROW IN NUMBER AND DIFFERENTIATE INTO VARIOUS TYPES OF TISSUES.

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18 Sample Injection Therapy Protocol 1. Blood Draw For smaller applications (e.g. foot, elbow, hand draw 22 cc of blood from patient Process blood in appropriate disposable to generate 3 ml of PRP For larger applications (e.g. shoulder, knee) draw of 60 cc blood from patient Process blood in appropriate disposable to generate 7-10 ml of PRP

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20 Protocol (con t) 2. Anesthetize skin and subcutaneous tissue Skin Apply to surface 1% Lidocaine spray to the skin or 1% solution of Xylocaine or Ethyl Chloride Subcutaneous Tissue Inject in and around treatment area Approximately 3 ml is used for small areas and 7 ml for larger joints (e.g. knee, shoulder) AVOID MARCAINE

21 Protocol (con t) 3. Using ultrasound guidance or other means (e.g. radiographic, palpation, clinical exam etc.), locate the area of concern (e.g. partial tear of tendon, frayed area of ligament. 4. THE MOST IMPORTANT DIAGNOSTIC AID IS ROAD TESTING THE PATIENT!!!!

22 ROAD TESTING THE PATIENT By road testing the patient we mean giving the patient lidocaine anesthetic in the in the area of pathology. If you are able to eliminate the patient s pain this is the area to inject the PRP. This technique should take precedence over over other diagnostic techniques.

23 INJECTION TECHNIQUES The injection technique depends upon the joint or tendon involved. For joints it is only necessary to place the PRP into the joint it will spread to the involved area on its own. For a tendon area it is best to inject the PRP into the tendon sheath and into the tendon itself in a peppering fashion. 23 gauge needle is ok to use

24 COMMON CONDITIONS TREATED WITH PRP 1. Disorders of the shoulder including bursitis and rotator cuff tears 2. Tendonitis of a variety of tendons including tennis elbow, Achilles tendonitis, and heel spur syndrome 3. Muscle tears, sprains, trigger points 4. Meniscus tears of the knee 5. Mild to moderate degenerative arthritis of various joints 6. Disorders of the spine

25 WHO IS NOT A CANDIDATE FOR PRP? 1. Various blood diseases 2. Consistent use of NSAIDS??? 3. Cortisone injection at the treatment site or systemic use of cortisone 4. Active cancers 5. infections

26 STEM CELLS

27 Stem Cells Stem cells are generally defined as 1. Undifferentiated cells that are capable of self-renewal through replication 2. Cells that differentiation into specific cell lineages Adult stem cells are necessary to maintain tissue and organ mass during normal cellular turnover.

28 A Few Common Terms Multipotent Descendents of pluripotent stem cells and antecedents of specialized cells in particular tissues. Cells yield a more restricted subset of cell lineages. Progenitor Cells Unipotent stem cells that can produce only one cell type. An early descendant of a stem cell that can only differentiate, it can no longer renew itself. Stromal Cells A mixed cell population that generates bone, cartilage, fat, and fibrous connective tissue, a.k.a. mesenchymal stem cells. Hematopoetic Cells Form all the types of blood cells in the body. Endothelial Cells Forms body s vasculature Plasticity The ability of stem cells from one adult tissue to differentiate into cell types of another tissue. Osteoprogenitor Cells Mesenchymal cells capable of differentiating into osteoblast cells. CD34 + Marker for the mononuclear cells

29 WHAT TYPES OF STEM CELLS EXIST? 1. Embryonic stem cells 2. Adult mesenchymal stem cells 3. Hematopoetic stem cells 4. IPS cells induced pluripotential stem cells 5. Various other more specific type of stem cells

30 EMBROYNIC STEM CELLS 1. By far the most controversial stem cells. U.S. government has lifted some bans but FDA has still significantly restricts use in people. 2 These cells seem to present the most potential for correcting and curing certain conditions due to their plasticity or ability to morph into many cell types. 3 There are ethical issues

31 POTENTIAL PROBLEMS WITH EMBRYONIC STEM CELLS 1. Patient will inherit any potential diseases that the embryo may have. 2. There is a significant potential that the cells can grow unchecked and essentially act as a tumor. 3. There are certain immunogenic factors. Will the body attack the stem cells as being foreign invaders? The patient may be required to take drugs to ward off cell rejection.

32 Hematopoietic Stem Cells

33 Hematopoietic stem cells 1, These are the cells that form blood products such as white and red blood cells. 2. They help establish a blood supply where there previously had not been one. 3. They have the ability to turn into other type of stem cells.

34 For hematopoetic stem cells it is best to stimulate their production and let the body deliver them to the involved areas by other methods (PRP and other stem cell injections)

35 HEMATOPOEIC STEM CELLS ARE OBTAINED BY APHERESIS The cost ( > $1000 ) of this procedure is not practical for most office based practices and these cells may not be best for clinical purposes.

36 ARE HEMATOPOIETIC STEM CELLS CAPABLE OF ACCOMPLISHING REPAIR OF OTHER TISSUES BESIDES =YES BLOOD TISSUE?

37 Stem Cell Mechanism of Action BM-MNC s Multipotent Stem Cell <0.001% of NC Stromal Stem Cells MCS CD 34 CD 45 - Plasticity Pre-osteoblasts Plasticity Endothelial progenitor cells Hematopoietic Stem Cells CD 34 +, CD % of NC Cytokines & Angiogenic Factors Both the stromal and hematopoietic stem cells work in concert to achieve tissue regeneration. The presence of hematopoietic stems cells augment the limited number of available stromal cells

38 IPS CELLS 1. THE PROBLEM WITH IPS CELLS IS THAT THEIR TELOMERES (DNA ENDS) ARE OLD AND SHORTENED. 2. THINK OF DOLLY THE CLONED SHEEP. DOLLY DIED AT A YOUNG AGE OF OLD AGE DUE TO THE FACT OF TELOMERE AGING. 3. THESE CELLS ARE PRODUCED FROM ADULT CELLS WHICH ARE MANIPULATED INTO BECOMING STEM CELLS BY ENZYMATIC OR VIRAL MEANS.

39 MESENCHYMAL STEM CELLS 1. These are stem cells that repair muscle, bone, cartilage, or tendons. 2. These are commonly called adult stem cells. 3. These stem cells are autologous meaning that they are from the same patient therefore no risk of genetic disease transmission. 4. These are the bodies repairmen 5. They act as construction managers helping other cells repair and build new tissue

40 MESENCHYMAL STEM CELLS THESE ARE THE MOST IMPORTANT CELLS FOR OUR PURPOSES!!!

41 ANY RISKS WITH MESENCHYMAL STEM CELLS? 1. Since these cells are the patients own there are minimal risks to the patient. 2. As of 2009 there are over 7000 studies on this cell line. 3. FDA states it is ok to use these cells as long as they are put back into the same patient and they are minimally manipulated.

42 HOW ABOUT GROWING THESE MESENCHYMAL CELLS IN THE LAB? 1. There are many studies that suggest that manipulating these cells outside the body such as culturing them can diminish their effectiveness!! 2. Some studies suggest that culturing the cells can lead to tumors. Probably effects telomeres. 3. Culturing the cells misses a host of other cells that are crucial in the overall repair process. 4. Not sure of status with FDA. They may consider these cells a drug.

43 WHERE DO MSCs LIVE? 1. Bone marrow 2. Fat cells especially lower abdominal fat. 3. Circulating blood ( not too many) 4. Joints very few

44 What type of stem cells are available for an office setting?

45 OFFICE STEM CELLS 1. HEMATOPEOTIC STEM CELLS 2. BONE MARROW (MESENCHYMAL) STEM CELLS 3. FAT (MESENCHYMAL) STEM CELLS

46 ADIPOSE STEM CELLS

47 FAT VS BONE MARROW

48 FAT CELLS VS BONE MARROW STEM CELLS

49 Adipose stem cells (ASC s) are the richest source of stem cells in the body. The adipose stem cells have the ability to differentiate into chondrocytes, fibrocytes etc. They seem to have many properties similar to mesenchymal stem cells. 1.(Kilroy et al Jour. of Cellular Phys. May 2007) 2. (Wu et all Stanford Univ. Sept 2009

50 FAT Cytokines High levels of: 1. Hepatocyte growth factor (HGF) major role in embryonic organ development, in adult organ regeneration and in wound healing 2. Vascular endothelial growth factor (VEGF) Stimulates growth of new blood vessels 3. Placental growth factor (PGF) Angiogenesis and vasculogenesis 4. Transforming growth factor-β (TGF) controls proliferation, cellular differentiation, and other functions in most cells. J Atheroscler Thromb Apr;13(2):77-81.

51 Current methods of obtaining adipose stem cells 1. CYTORI SYSTEM 2. TISSUE GENESIS SYSTEM 3. SIMPLE LIPOSUCTION TECHNIQUE 4. SIMPLE LIPOSUCTION COMBINED WITH STEM CELL EXTRACTION TEHNIQUE

52 Cytori Celution and Tissue Genesis Systems Cost is high for most office based practices. The system prepares the graft for injection. Not much work for the lab tech.

53 SIMPLE LIPOSUCTION TECHNIQUE 1. THIS SYSTEM IS SIMPLE, COST EFFECTIVE, SAFE, AND REQUIRES MINIMAL LEARNING AND TIME INVESTMENT. 2. THE TOTAL COST FOR THIS SYSTEM IS IS APPROX. $10-15

54 FAT STEM CELL (SVF) ISOLATION THIS IS A PROCESS THAT UTILIZES CELL WASHINGS, CENTRIFUGATION, AND ENZYMATIC DIGESTION. THIS PROCESS EXTRACTS THE STEM CELLS FROM THE FAT PRODUCING MILLION STEM PER CASE. TYPICALLY 50 CC. OF FAT TISSUE PRODUCES 1-2 CC. OF SVF OR FAT STEM CELLS. THIS HAS BECOME ONE OF OUR MOST FREQUENT PROCEDURES.

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56 LIPOSUCTION TECHNIQUE

57 ANESTHESIA FOR LIPOSUCTION

58 SIMPLE LIPOSUCTION TECHNIQUE

59 FAT CELLS SEPARATING

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62 HOW ARE FAT STEM CELLS RELEASED FROM FAT TISSUE? 1. THIS IS ACCOMPLISHED BY THE CYTOKINES AND GROWTH FACTORS FOUND IN THE PRP WHICH ARE RELEASED BY THE PRP. 2. THIS PROCESS RELEASES THE FAT STEM CELLS FROM THE FAT TISSUE. THE REMAINING TISSUE ACTS AS A SCAFFOLD.

63 OTHER PURPOSE OF FAT CELLS IN ADDITION TO ACTING AS A SOURCE OF STEM CELLS WE USE A FAT GRAFT IN JOINTS AND CERTAIN SOFT TISSUE INJURIES AS A SCAFFOLD. THE FAT GRAFT ALLOWS STEM CELLS AND OTHER CELLS TO ADHERE TO IT AS A SCAFFOLD.

64 BONE MARROW STEM CELLS

65 THE TECHNIQUE FOR OBTAINING BONE MARROW STEM CELLS IS A SIMPLE ASPIRATION MUCH AS A HEMATOLOGIST DOES.

66 ONLY NECESSARY TO USE LOCAL ANESTHESIA TO ANESTHETIZE THE PERIOSTEUM

67 TYPICALLY REMOVE ABOUT 60CC OF BONE MARROW ASPIRATE

68 OBTAINING BMAC

69 ASPIRATION OF BMAC

70 ASPIRATION OF BMAC

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72 REMEMBER STEM CELLS NEED PRP FOR ACTIVATION

73 FATHER TIME TAKES HIS TOLL ON MESENCHYMAL STEM CELLS

74 POINTERS FOR OBTAINING BONE MARROW STEM CELLS 1. WHEN DRAWING BONE MARROW ASPIRATE DO IT SLOWLY!!!!!!!! 2. REMEMBER THAT BONE MARROW ASPIRATE CONTAINS PRP

75 SUBSEQUENT INJECTIONS AT ONE MONTH INTERVALS PATIENT WILL BE GIVEN PRP INJECIONS WITH HGH. THE INJECTIONS NUMBER BETWEEN 2-3. The stem cells last about 3-4 months in the joint while the platelets about 6 weeks. During the entire time from start to finish patient is to take a variety of supplements.

76 WHAT OTHER MATERIALS ARE INJECTED WITH THE STEM CELLS?

77 HUMAN GROWTH HORMONE(HGH) 1. Dr. Allan Dunn has shown that HGH will absolutely cause tissue such as cartilage to grow by injecting it into joints. 2. Little in the way of side effects since this is injected into the joint and not that much is absorbed into the rest of the body. 3. Not used in professional athletes. 4. Usual dosage is 0.2mg of HGH ( I use Omnitrope from Sandoz).

78 DEXAMETHASONE WITH JOINT INJECTIONS WE WILL USE 10 NANNOGRAMS OF DEXAMETHASONE WHICH IN THIS DOSE ACTS AS A GROWTH FACTOR

79 SUPPLEMENTS? SUPPLEMENTS APPEAR TO BE IMPORTANT IN INCREASING STEM CELL PRODUCTION IN THE BODY. WE CURRENTLY USE NATURACELL AND THE LONGEVITY FACTORS. ALL PATIENTS ARE PLACED ON THESE SUPPLEMENTS. THESE SUPPLEMENTS ARE USED ON BOTH PRP AND STEM CELL INJECTIONS.

80 CALCITONIN 1. WHEN DEALING WITH ANY JOINT PROBLEM ALL PATIENTS ARE PLACED ON CALCITONIN NASAL SPRAY FOR ONE OR TWO MONTHS. 2. THIS HELPS STABILIZE ARTHRITIC LESIONS AND UNDERLYING BONE. THIS APPEARS TO MINIMIZE DJD DAMAGE

81 HYALURONIC ACID THERE APPEARS TO BE EVIDENCE THAT HYALURONIC ACID MAY ENHANCE THE FUNCTION OF STEM CELLS IN THE JOINT. ( Saw et al paper presented at British Orthopedic Association Meeting Sept 2009)

82 HYALURONIC ACID AND STEM CELLS SAW ET AL PERFORMED MICROFRACTURE SURGERY IN KNEES. ONE WEEK AFTER SURGERY THEY INJECTED PERIPHERIAL BLOOD STEM CELLS (2.5MG) MIXED WITH 2ML OF HYALURONIC ACID AND PERFORMED 5 WEEKLY INJECTIONS OF THIS MIXTURE. THEIR BIOPSY RESULTS SHOWED HYALINE CARTILAGE REGENERATION!

83 HYPERBARIC OXYGEN A NUMBER STUDIES SUGGEST HYPERBARIC OXYGEN WILL MOBILIZE STEM CELLS IN THE BODY MAKING THEM AVAILABLE FOR REPAIR. THIS APPEARS TO INCREASE NITRIC OXIDE PRODUCTION WHICH DIRECTLY INCREASES STEM CELL PRODUCTION AND RELEASE.

84 BIONICARE BRACE 1. Zizic, et. al. The treatment of OA of the knee with pulsed electrical stimulation. Journal of Rheumatology Mont/Hungerford Abstract The use of PES to defer total knee arthroplasty (TKA) inpatients with OA of the knee. Presented at American Academy of Orthopaedic Surgeons Annual Meeting, March 2004.

85 BIONICARE BRACE IT APPARENTLY UPREGULATES CHONDROCYTES TO REPRODUCE MUCH IN THE SAME WAY STEM CELLS AFFECT SURROUNDING CELLS. OUR CENTER IS CURRENTLY DOING A STUDY WITH THIS BRACE AND STEM CELLS.

86 PHOTO MODULATION PHOTO MODULATION SEEMS TO WORK ON BOTH PRP COMPONENTS AND STEM CELLS

87 Research-Why it Works Stem Cells Respond to Low Level Lasers Photomedicine and Laser Surgery Volume 27, Number 2, 2008 Mary Ann Liebert, Inc. Pp DOI: /pho Implantation of Low- Level Laser Irradiated Mesenchymal Stem Cells into the Infarcted Rat Heart Is Associated with Reduction In Infarct Size and Enhanced Angiogenesis Hana Tuby, M.Sc., Lidya Maltz, M.Sc., and Uri Oron, Ph.D.

88 Photoactivated PRP 1. PRP plus Autologous conditioned serum 2. Healing and anti-inflammatory 3. - growth factors from platelets (healing) 4. - IL1ra from WBCs (potent antinflammatory) 5. - beta-endorphin from WBCs (pain relieving) 6. - pro-inflammatory cytokine receptor shedding from WBCs (anti-inflammatory)

89 WHO IS NOT A CANDIDATE FOR STEM CELL INJECTIONS. 1. Bone marrow derived cancers such as lymphoma etc. If other cancer history is present but cured than no need to worry. However HGH is used on a case by case basis. 2. Severe anemia or other blood problems 3. Active infections

90 WHAT MUST BE AVOIDED 1. NSAIDS??? AND CORTISONE 2. MINIMAL ALCOHOL INTAKE 3. INACTIVITY 4. COUMADIN OK AND ASPIRIN OK IF NEEDED FOR HEART PROBLEMS 5. PLAVIX DOES NOT SEEM TO BE A PROBLEM

91 STEM CELL VS. PRP INJECTIONS 1. Stem cell injections more important in areas of low oxygen content (bone marrow is a low oxygen environment) such as a severely arthritic joint or disc. 2. Stem cells alone in an area will remain inactive unless they are in an environment of platelets whose growth factors activate the stem cells

92 BONE MARROW VS FAT STEM CELLS EACH HAS IT S PURPOSE. BMAC HAS MANY DIFFERENT GROWTH FACTORS AND APPROXIMATELY THE SAME NUMBER OF TOTAL STEM CELLS. BUT SVF HAS MORE MESENCHYMAL STEM CELLS. IF POSSIBLE USE BOTH OTHERWISE LEAN TOWARD SVF DUE TO THE COST INVOLVED AND NUMBER OF MESENCHYMAL STEM CELLS PRODUCED.

93 HOW LONG BEFORE RESULTS ARE SEEN? 1. This varies with the patient s age, the condition being treated, severity of the condition etc. Some results can be seen in as little as two weeks. 2. Tell your patients to expect a rollercoster effect. 3. Some patients report pain can leave as if a light switch were turned off

94 RESULTS WE HAVE PERFORMED APPROXIMATELY 3500 INJECTIONS IN OUR CLINIC. THESE INCLUDE BOTH PRP AND BMAC INJECTIONS. WE HAVE PERFORMED 650 BMAC INJECTIONS, 2675 PRP INJECTIONS AND 225 SVF INJECTIONS. APPROXIMATELY 66% OF THE PRP INJECTIONS WERE PERFORMED WITH FAT GRAFTS.

95 BMAC CASES CASES WERE PERFORMED FOR OSTEOARTHRITIS OF THE KNEE CASES FOR OSTEOARTHRITIS OF THE HIP CASES FOR OSTEOARTHRITIS OF THE SHOULDER 4. ALL BMAC CASES WERE PERFORMED WITH FAT GRAFTS AND 90% HAD HGH INJECTION.

96 RESULTS IN BMAC CASES 1. KNEES REPORTED APPROXIMATELY 88% EXCELLENT RESULTS. 2. HIPS REPORTED APPROXIMATELY 82% EXCELLENT RESULTS. 3. SHOULDERS REPORTED 80% EXCELLENT RESULTS. 4. AN EXCELLENT RESULT WAS A SIGNIFICANT CHANGE IN PRE INJECTION PAIN AND INCREASE IN ACTIVITIES. WE LOOKED FOR AT LEAST 80% IMPROVEMENT IN PAIN SCORES

97 RESULTS IN PRP CASES 1. KNEES = 1250 CASES INCLUDING DJD, MENISCUS TEARS, ACL TEARS AND AVN. 2. HIPS = 400 CASES INCLUDING DJD, LABRAL TEARS, AND AVN. 3. SHOULDERS = 600 CASES INCLUDING ROTATOR CUFF TEARS, LABRAL TEARS, AND DJD OF JOINT. 4. VARIOUS TENDONS INCLUDING ACHILLES, EPICONDYLITIS (BOTH MEDIAL AND LATERAL) AND OTHER TENDONS ABOUT THE BODY. 5. APPROXIMATELY 66% OF THE PRP CASES WERE PERFORMED WITH FAT GRAFTS AND 90% RECEIVED HGH.

98 RESULTS IN PRP CASES THE RESULTS IN THE PRP CASES MORE OR LESS MIRROR THE RESULTS OBTAINED IN THE BMAC CASES. IN GENERAL THE CASES DONE WITH THE PRP TYPICALLY WERE NOT AS SEVERE AS THOSE IN THE BMAC SERIES.

99 RESULTS OF BMAC AND SVF COMBINED 1. IT APPEARS TOO SOON TO SAY DEFINITIVELY BUT WE SEEM TO BE HAVING THE BEST RESULTS WITH THESE TECHNIQUES COMBINED. 2. PATIENTS ARE HAVING LESS PAIN EARLIER. 3. SEEMS TO BE LESS NEED FOR REPEAT PRP INJECTION

100 SVF ALONE 1. THE RESULTS WITH SVF AND PRP SEEM TO RIVAL THE RESULTS WITH BMAC, PRP AND FAT GRAFT. 2. SVF SEEM TO WORK FASTER POSSIBLY SECONDARY TO THE GREATER NUMBER OF INJECTED MESENCHYMAL STEM CELLS WITH SVF. 3. STILL TO EARLY TO SAY FOR SURE

101 CURRENT STUDIES CLINIC IS INVOLVED IN 1. HYALURONIC ACID AND STEM CELLS 2. BIONICARE ELECTRICAL BRACE 3. VARIOUS SUPPLEMENTS 4. HYPERBARIC OXYGEN

102 THANK YOU