Stem cells

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Evolving treatment in Medicine

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By: acortho (8 month(s) ago)

U can download, Pl acknowledge. AC

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hello sir, my name is ramesh rathod doing Ph.Dat bangalore. will u please help me to email some ppts on stem cell in clinical application, as it is my topic of reserch. thanking u.

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STEM CELL THERAPY IN ORTHOPAEDIC SURGERY : 

STEM CELL THERAPY IN ORTHOPAEDIC SURGERY Dr.A.Chandrasekaran, Ph.D., Dr. Solomon Paul, Ph.D., Dr. P. Venkatachalam, Ph.D., Mr. U Baraneedharan,( Ph.D.,) Sri Ramachandra University, Porur, Chennai 116. INDIA

Stem cell : 

Stem cell 2001 sequence of the human genome Stem cells hold promise for unlocking life-saving secrets

Stem cells : 

Stem cells “Stem Cells: Hype or Hope?”

Stem cell - HOPE : 

Stem cell - HOPE Development of region specific stem cell in treating difficult Orthopaedic problem for which there is no standard treatment available now. To do away animal experiments To establish “Stem cell Bank”

Stem cells : 

Stem cells self-renewal and to differentiate into various types of tissues under certain conditions. regenerate new tissues and repair organs hold tremendous promise for the treatment of many serious diseases and injuries.

Stem cell : 

Stem cell

Different types of Stem cells : 

Different types of Stem cells Classified depending upon the source –

Embryonic stem cell : 

Embryonic stem cell

Nuclear transfer in stem cell : 

Nuclear transfer in stem cell A pluripotent stem cell (iPSC) was created by the insertion of four transcription factors (Oct4, Klf4, Sox2 and c-Myc) into mouse skin fibroblasts . Takahashi K, Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006. 126: 663-76.

Stem cell plasticity : 

Stem cell plasticity

Bone Marrow Stem cells : 

Bone Marrow Stem cells Marrow stem cells Hematopoietic stem cell CD34 “+” Cells Abundant cells Progenitors Non Adherent Mesenchymal stem cell CD34 “–” Cells Rare cells Total undifferentiated Adherent

Bone marrow stem cells : 

Bone marrow stem cells

Mesenchymal stem cells (MSC) : 

Mesenchymal stem cells (MSC) Most commonly used These are non hematopoietic exhibit multi lineage differentiation capacity, can give rise to diverse tissues, including bone, cartilage, adipose tissue, tendon and muscle.

Mesenchymal stem cells : 

Mesenchymal stem cells

Stem cells : 

Stem cells MSC Colony on day 05 Confluent Monolayer on day 15 Isolation and in vitro expansion of mesenchymal stem cells

Alizarin Red Staining- 21 days : 

Alizarin Red Staining- 21 days Control - Undifferentiated cells Differentiated cells - Nodulation 10 X 10 X

Osteoblast differentiation : 

Osteoblast differentiation Differentiation was seen as early as the first week of induction Cells became flattened and showed calcium deposition and could be seen as nodules, by the formation of mineralized matrix

Chondrogenic differentiation : 

Chondrogenic differentiation Control – Undifferentiated cells Chondrocyte – differentiated cells 10 X

Adipogenic differentiation : 

Adipogenic differentiation Control – Undifferentiated cells Adipocytes – differentiated cells 20 X

Skeletal myoblast differentiation : 

Skeletal myoblast differentiation Myotube formation 20 X 20 X

Advantages of Mesenchymal Stem cells : 

Advantages of Mesenchymal Stem cells Autologous – harvested from the patient themselves No major ethical constraints – unlike embryonic stem cells Can be expanded in vitro – unlimited supply of therapeutic cells. Does not express HLA II antigens – Allo-transplantation is possible. Strong evidence for In Vitro and In Vivo differentiation

Stem cell in Orthopaedics : 

Stem cell in Orthopaedics The challenge in orthopaedics is to regenerate and repair damaged or diseased musculoskeletal tissues.

Stem Cells -Orthopaedics : 

Stem Cells -Orthopaedics Critical bone defects and non-unions Avascular necrosis Cartilage repair Ligament and tendon injuries Spinal cord regeneration Intervertebral disc degeneration Muscular dystrophies

Bone : 

Bone MSCs can be used to enhance bone regeneration and union in cases of critical bone defect, non-union, physis regeneration in children and to improve bone quality in osteogenesis imperfecta Lee EH, Hui JH. The potential of stem cells in orthopaedic surgery. J Bone Joint Surg 2006; 88(7): 841-51. Pereira RF, O'Hara MD, Laptev AV, Halford KW, Pollard MD, Class R, Simon D, Livezey K, Prockop DJ. Marrow stromal cells as a source of progenitor cells for nonhematopoietic tissues in transgenic mice with a phenotype of osteogenesis imperfecta. Proc Natl Acad Sci USA 1998; 95:1142-7.

Cartilage : 

Cartilage Autologous Chondrocyte implantation (ACI) is a biological attempt to regenerate normal articular cartilage. Transplantation of Autologous uncultured bone marrow-derived mononuclear cells contributes to articular cartilage repair has clinical potential. Awad HA, Boivin GP, Dressler MR, Smith FN, Young RG, Butler DL. Repair of patellar tendon injuries using a cell-collagen composite. J Orthop Res 2003; 21(3): 420-31. Young RG, Butler DL, Weber W, Caplan AI, Gordon SL, Fink DJ. Use of mesenchymal stem cells in a collagen matrix for Achilles tendon repair. J Orthop Res 1998;16(4):406-13.

Tendons and Ligaments : 

Tendons and Ligaments Application of a collagen gel loaded with MSCs in a rabbit Achilles and patellar tendon defect resulted in improvement of structure, biomechanics, and function The use of synovial MSCs into a bone tunnel from the tibial plateau to the tibial tuberosity showed accelerated tunnel healing and early remodeling of tendon-bone junction Ju YJ, Muneta T, Yoshimura H, Koga H, Sekiya I. Synovial mesenchymal stem cells accelerate early remodeling of tendon-bone healing. Cell Tissue Res 2008; 332(3): 469-78. Epub 2008.

Meniscus : 

Meniscus MSCs has also shown improvement in meniscal wound healing; even in avascular areas, there was production of an abundant extracellular matrix contributed to meniscal repair Abdel-Hamid M, Hussein MR, Ahmad AF, Elgezawi EM. Enhancement of the repair of meniscal wounds in the red-white zone (middle third) by the injection of bone marrow cells in canine animal model. Int J Exp Pathol 2005; 86(2): 117-23. Izuta Y, Ochi M, Adachi N, Deie M, Yamasaki T, Shinomiya R. Meniscal repair using bone marrow-derived mesenchymal stem cells: experimental study using green fluorescent protein transgenic rats. Knee 2005; 12(3): 217-23.

Meniscus : 

Meniscus Isolated and expanded human Autologous MSCs could effectively regenerate cartilage and meniscal tissue when percutaneously injected into knees . Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D. Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician 2008; 11(3): 343-53.

Muscles and Skin : 

Muscles and Skin Intravenous injection of MSCs in models of immuno deficient mice with Duchene Muscular Dystrophy has shown differentiation of MSCs into muscle fibers and partial restoration of dystrophin expression Gussoni E, Soneoka Y, Strickland CD, Buzney EA, Khan MK, Flint AF, Kunkel LM, Mulligan RC. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature. 1999; 401(6751): 390-4. MSCs helps in healing of chronic skin wounds . Badiavas EV, Falanga V. Treatment of chronic wounds with bone marrow-derived cells. Arch Dermatol 2003; 139(4): 510-6.

Spine, Spinal Cord and Neural Tissues : 

Spine, Spinal Cord and Neural Tissues MSCs isolated in culture from the mononuclear layer of bone marrow can remyelinate, damaged spinal cord axons after direct injection into the lesion. Stem cells alone may not be enough to improve function in a damaged spinal cord Akiyama Y, Radtke C, Honmou O, Kocsis JD. Remyelination of the spinal cord following intravenous delivery of bone marrow cells. Glia. 2002; 39: 229-36.

Peripheral nerves : 

Peripheral nerves MSCs can differentiate into neurons and glia Kabos P, Ehtesham M, Kabosova A, Black KL, Yu JS. Generation of neural progenitor cells from whole adult bone marrow. Exp Neurol 2002; 178(2): 288-93.

Intervertebral disc : 

Intervertebral disc Cell transplantation can potentially increase proteoglycan production, induce disc regeneration or slow the process of degeneration Transplantation of autologous disc cells and Chondrocyte derived from costal cartilage has been demonstrated to slow disc degeneration Brisby H, Tao H, Ma DD, Diwan AD. Cell therapy for disc degeneration: potentials and pitfalls. Orthop Clin North Am 2004; 35:85-93.

Stem cell in large defect : 

Stem cell in large defect

Our Thanks : 

Our Thanks Shri. Abhaikumar, Tricell, SRU.

Case study 1 : 

Case study 1 25 years male Traffic accident 2yrs 6mths back Lost other limb above knee Allograft failed 20 cm gap

Allograft : 

Allograft

After allograft : 

After allograft 20 cm gap Tibialisation of fibula Segmental transfer

Segmental transportation : 

Segmental transportation

Rapid transportation : 

Rapid transportation

Regenerate : 

Regenerate

Ethical issues : 

Ethical issues When adult stem cells are used taken from the patient himself no ethical issues can rise

Ethics : 

Ethics The patient’s safety and well-being must always come first. As pointed out by Lau et al many of the advertised stem cell treatments on the Internet are not evidence-based. Patients must be protected from exploitation by such unscrupulous practices Lau D, Ogbogu U, Taylor B, Stafinski T, Menon D, Caulfield T. Stem Cell Clinics Online: The Direct-to-Consumer Portrayal of Stem Cell Medicine. Cell Stem 2008 4; 3(6): 591-4.

Conclusion : 

Conclusion MSC’s is a very promising tool for regenerative medicine Further engineering such osteogenic cells in scaffolds would allow us to transplant and repair bone defects. Cord blood is generally used for haemopoietic disorders and not in musculoskeletal tissues.

References : 

References The ISSCR Guidelines for the Clinical Translation for Stem Cells and the 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: http://www.isscr.org/clinical_trans/ 56. International Society for Stem Cell Research. Patient Handbook on Stem Cell Therapies, 2008 Dec 3; Available from: http://www.isscr.org/clinical_trans