STEM CELLS. Dr Mohammad Ashfaq Konchwalla Consultant Orthopaedic Sports Surgeon

Transcription

1 STEM CELLS Dr Mohammad Ashfaq Konchwalla Consultant Orthopaedic Sports Surgeon

2 PRACTICE SAUDI GERMAN HOSPITAL, DUBAI MEDCARE HOSPITAL, DUBAI

3 Totipotent cells are cells that can develop into all cell types in the human body and can also form extra embryonic and placental cells Pluripotent cells are cells that can develop into cells of all the three germ layers (endoderm, mesoderm or ectoderm). Multipotent cells are cells that can develop into more than one but not all germ layers E.g. adult stem cells and cord blood cells

4 Type of stem cells Embryonic (also called pluripotent ) stem cells are capable of developing into all the cell types of the body. Adult stem cells are less versatile and more difficult to identify, isolate, and purify.

5 SOURCE OF STEM CELLS Stem cells can be derived from the following sources: Allogenous Autogenous Xenogenic

6 Stem cells can be obtained from: Bone marrow Adipose tissue Placenta Blood Umbilical cord Human amniotic fluid Dental pulp Synovial fluid Skin Skeletal muscle

7 STEM CELLS Undeveloped biological cells capable of: Proliferation Self-renewal Conversion to differentiated cells Regenerating tissues

8 Isolation of stem cells Stem cells can be unselected cells obtained from bone marrow after centrifugation or selected and enhanced in culture utilising their affinity to tissue plastics

9 Mechanism of action Differentiate into bone, muscle, cartilage, ligament or tendon cells Paracrine effects: secrete growth factors and cytokines e.g. BMPs, TGF beta and VEGF Result in angiogenesis, repair, cell survival and proliferation

10 Bone Marrow Stem Cells Bone Natural killerf* (NK) cell ^ Lymphoid progenitor T lymphocytes Neutrophil r Hematopoetic stem cell I Multi potential stem cell Stromal Osteoblast^ stem cell ^ B lymphocyte Myeloid n Pre-osteoblast Skeletal muscle stem cell? progenitor ce Platelets^ v 'Red blood cells Hematopoetic Marrow supportive stroma adipocyte Bone (or cartilage) Lining Hepatocyte stem cell? cell.osteocyte Hematopoetic stem cell

11 Hematopoietic stem cells Hematopoietic Stem Cells Lymphoid Hematopoietic Progenitor Coll Stem Ce Gone Manfiw Mult.ipotent.iah Stem cell Basophil Eosinophil NeutrOohl Myeloid Progenitor Coll Monocyte/ Macrophage Red B ood Ce s

12 Mesenchymal Tissue Bone Marrow/Periosteum THE MESENGENIC PROCESS CO Mesenchymal Stem Cell (MSC) Proliferation MSC Proliferation Commitment Lineage Progression Osteogenesis Chondrogenesis 0 1 Transitory Osteoblast O 1 Osteoblast Differentiation 300 Maturation 0? 1 Transitory Chondrocyte 9 Chondrocyt e rjr^ Myogenesis Marrow Stroma., en<^ 9 enes i s/ 1 Ligamentogenesis Myoblast \ Myoblast Fusion 0 Transitory I Stromal Cell 0 i Unique Micro-niche Adipogencsis Other 0 i Transitory jbroblast o O i I early adipocyte I l I Osteocyte Hypertrophic Chondrocyte Myotube Stromal Cells T/L Fibroblast... Dermal and Adipocyte other Cells BONE CARTILAGE MUSCLE MARROW TENDON/ ADIPOSE CONNECTIVE LIGAMENT TISSUE TISSUE

13 Stem cell application

14 Stem cell treatments.svg Wikipedia

15 Stem cells in Orthopaedics Avascular necrosis Critical bone defects and non-unions Cartilage repair - acute Spinal cord injury - acute / chronic Intervertebral disc regeneration Articular cartilage regeneration Rheumatic and Rheumatoid disorders Inflammatory autoimmune disorders Osteogenesis Imperfecta Duchene Muscular Dystrophy

16 Mesenchymal stem cell / MAK Experience Knee Microfracture and MSC 54 Scaffold and MSC 20 AVN of Hip and MSC 24 Hip Arthroscopy labrum repair/msc 36 ACL and MSC 48 Menisci repair and /MSC 26 Rotator cuff repair/msc 35 Ankle Microfracture /MSC 14

17 Marrow aspiration parallel aspiration divergating technique

18 Regen lab system for bone stem cells

19 VIDEOS

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21 STEM CELLS IN CARTILAGE REPAIR & ARTHRITIS

22 Stem Cells in OA Normal Anabolic Joint Many Stem Cells to Keep Up with Daily Maintenance Abnormal Catabolic Joint Few Functional Stem Cells to Keep Up with Daily Maintenance

23 Mesenchymal stem cells in arthritic diseases MSCs possess potent immunosuppression and anti-inflammation effects through secretion of various soluble factors, MSCs can influence the local tissue environment and exert protective effects with an end result of effectively stimulating regeneration in situ. Can be used for therapeutic application in degenerative joint diseases such as RA and OA. Faye H Chen and Rocky S Tuan Arthritis Research & Therapy 2008,10:223 (doi: /ar2514)

24 Osteochondral Lesions of the Knee Mesenchymal stem cells represent 2% to 3% of the total mononuclear cells in bone marrow and have the ability to differentiate into various lineages, including osteoblasts and chondroblasts. The rationale of the ''one-step technique'' is based on the idea of transplanting the entire bone-marrow cellular pool instead of isolated and expanded mesenchymal stem Cells. Osteochondral Lesions of the Knee: A New One-Step Repair Technique with Bone-Marrow-Derived Cells. By Roberto Buda, MD, Francesca Vannini, MD, PhD, Marco Cavallo, MD, Brunella Grigolo, PhD, Annarita Cenacchi, MD, and Sandro Giannini, MD J Bone Joint Surg Am. 2010;92Suppl 2:2-11 d doi: /jbjsj.00813

25 Stem cells in cartilage repair & arthritis Buda et al. (2010) used MSCs for the treatment of osteochondral lesions of femur and talus. They reported satisfactory clinical results and integration of cells in defects in both types of osteochondral lesions. Thus, use of MSCs in cartilaginous lesions has come to the clinical stages from experimental stages and the results have been encouraging.

26 Cartilage & arthritis Abrasion chondroplasty in which drill holes are made into the cartilage to allow for the subchondral bone marrow to come out and layer the cartilage defects have shown good results. Such a procedure is followed by formation of fibro-cartilage at the cartilage defect site.

27 Knee arthroscopy: microfracture and stem cell

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29 ACI MACI

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31 Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: A proof of concept trial

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35 MESENCHYMAL STEM CELL INCREASE CHONDROCYTES PROLIFERATION

36 Mscs as progenitor cells to engineer cartilage implants that can be used to repair chondral and osteochondral lesions, or as trophic producers of bioactive factors to initiate endogenous regenerative activities in the OA joint. Targeted gene therapy might further enhance these activities of mscs.

37 MESENCHYMAL STEM CELL

38 2 ND GENERATION CELL THERAPIES Autogenous cells Seeded scaffold or liquid gel Minimizes periosteal related complications Allows arthroscopic implant

39 Autogenous Allogeneic Time =O decision making May use scaffold/ staple May implant in fibrin glue MINCED CARTILAGE Fragments + Scaffold

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41 3 RD GENERATION CELL BASED Autogenous Allogeneic 3-D cartilage graft Technical ease might allow arthroscopic insertion with Bioadhesive

42 OTHER SYNOVIAL FLUID FACTORS: Growth factors: -IGF-1, FGF, tg-beta super family Can we stimulate these to increase GAG synthesis after cartilage injury Catabolic factors: cytokines: - IL-1, TNF, IL-6,7,8 Can we inhibit these to avoid matrix breakdown after cartilage injury

43 HIP ARTHROSCOPY: AVN AND BONE STEM CELLS

44 SHOULDER ARTHROSCOPY AND STEM CELL INJECTION

45 ELBOW ARTHROSCOPY

46 ANKLE ARTHROSCOPY: STEM CELL INJECTION

47 ACL /MSC

48 KNEE ARTHROSCOPY: STEM CELL INJECTION IN THE MENISCI

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50 Conclusion Stem cell therapy is as an attractive option for the treatment of intractable diseases. Its use is based on sound biological principles. Many of these studies have shown good results but at the same time many have shown failures. This might also be linked to the patient selection, the type of cells used, the concentration of cells used, the method of application, duration of follow up and evaluation tools among others.

51 References ISSCR Guidelines for the Clinical Translation for Stem Cells Patient Handbook on Stem Cell Therapies provide the requisite information for the clinical use of stem cells International Society for Stem Cell Research. Guidelines for Clinical Translation of Stem Cells, 2008 Dec 3; Available from: International Society for Stem Cell Research. Patient Handbook on Stem Cell Therapies, 2008 Dec 3; Available from:

52 THANK YOU