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Cartilage Repair using Stem cell & Orthobiologics
 

Cartilage Repair using Stem cell & Orthobiologics

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Regenerating Cartilage is a challenge. What's new in this field of cartilage regeneration and the current status of the stem cell use in this field is described.

Regenerating Cartilage is a challenge. What's new in this field of cartilage regeneration and the current status of the stem cell use in this field is described.

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  • These are the principles of chondrogenesis.

Cartilage Repair using Stem cell & Orthobiologics Cartilage Repair using Stem cell & Orthobiologics Presentation Transcript

  • Cartilage Regeneration: A challenge in OA KNEE Dr Vaibhav Bagaria MBBS MS FCPS Arthroplasty & Sports Surgeon: Visiting Arthroplasty Surgeon: CARE hosp & ORIGYN, Nagpur Apollo Hospital, Noida & Columbia Asia Hospital, GZB
  • A ‘Good Start’ Dr Jain ? CAD 2012 Mumbai, India  To recreate what God has created?  Cartilage regeneration In ‘Arthroplasty’ Meeting
  • Cartilage Cartilage consists of cells called chondrocytes and extensive extracellular matrix rich in glycoaminoglycans, proteoglycans and collagens. 3 forms of cartilage • hyaline cartilage (articular joints, type 2 collagen) • fibrocartilage (meniscus, intervertebral discs, type 1 collagen) • elastic cartilage Cartilage is avascular tissue with low number of cells with poor proliferation capacity. Damaged cartilage does not self-regenerate and is a major cause of joint disease i.e. osteoarthritis.
  • The challenge is to engineer cartilage that is biochemically, structurally and biomechanically similar to normal cartilage Growth factor/peptide Efficient cartilage repair Scaffold Cells • • • • • Bioactive factors Extracellular matrix Scaffold/delivery system Mechanical stimulation Genetic manipulation site/tissue specific cartilage
  • OA KNEE  Cartilage damage in osteoarthritis is widespread and lesions are large  Mechanical abnormalities -> cause localized regions of dynamic loading stress  local environment -> presence of signals which promote inflammation, suppress cartilage matrix synthesis and enhance matrix degradation.  Paradoxically, endogenous stem-cell like progenitor cells with chondrogenic potential found which is not present in normal cartilage
  • Cellular based therapy  Adult Chondrocyte  Adult Mesenchymal Stem cell  Human Embryonic Stem Cell  Inducible Progenitor stem cell
  • Adult chondrocyte based therapy  A preventative strategy to repair articular cartilage damage following acute injury  Using cartilage grafts or implanted chondrocytes to replace focally damaged lesions  limited to repair of localized articular cartilage injury in healthy and relatively young patients not for the typical OA with more widespread damage.  OATS -> ACI -> MACI -> HACI (hyaluronan scaffold) -> CCI ( characterized by chondrogenic markers)
  • Cartilage repair FIRST GEN Attempts to regenerate articular cartilage have been introduce in clinical practice with autologous chondrocytes implantation (ACI) Cell expansion Brittberg M et al (1994) N. Engl J Med  > 70% cases of repair Since its introduction, ACI has become a widely applied surgical method with good to excellent clinical outcomes.
  • Stem cells neural retinal stem cellll liver indefinite self renewal beta cell progenitorit or cell limited self renewal intestinal differentiation blood mesenchymal amniotic hES testicular skin
  • Stem Cells Pluripotent: Embryonic Stem Cells (ESCs), Induced Pluripotent Stem Cells (iPSCs) Multipotent: Adult Stem Cells, e.g. Bone marrow derived Stem Cells (BMSCs), Fat-derived Stem Cells (ADSCs), others
  • Adult Mesenchymal stem cell based therapy  Mesenchymal Stem Cells (MSC) can be obtained from bone marrow, synovium, fat, or umbilical cord.  Distinct potential for differentiation into the chondrogenic lineage.  Adipocyte-derived MSC have been suggested to be most chondrogenic  May be differentiated into chondrocytes using growth factors such as (BMP) (IGF) (FGF], or using scaffolds [40] which may release prochondrogenic signals such as TGF-β
  • Source of Stem Cell Fat (AMSC) or Bone Marrow (BMSC) ?
  • Bone marrow mesenchymal stem cell www.abcam.com
  • Principles of Chondrogenesis  2mm burr/drill  Depth 5 to 10mm  1 to 2mm gaps  Light burring in between drill holes  Correct mal-alignment  Treat associated injuries  AMSC + Matrix  Intra-articular injections  CPM  Rehab protocol
  • Technique Bone Marrow Aspiration Concentration Seeding
  • Arthroscopy
  • Adapted from Dr Khay-Yong SAW, KLSMC
  • Drilling Drilling Drilling Drilling Drilling Drilling
  • Blood clot scaffold
  • References:
  • hESC- Human Embryonic Stem Cells  Limitless no. of cell with chondrogenic potential.  Protocols have been defied; most commonly using BMP, involve an intermediate stage – Embryoid body formation.  Encouraging results in vivo in rat and other animal models.  Safety: ? Teratoma, Xenogenic contamination, Immune rejection( caritlage immune privileged site).  Ethical issues loom large! Gong G, Ferrari D, Dealy CN, Kosher RA (2010) Direct and progressive differentiation of human embryonic stem cells Toh WS, Lee EH, Guo XM, Chan JK, Yeow CH, et al. (2010) Cartilage repair using hyaluronan hydrogel-encapsulated human embryonic stem cell-derived chondrogenic cells. into the chondrogenic lineage. J Cell Physiol 224: 664-671. Biomaterials 31: 6968-6980.
  • iPSC – Inducible Progenitor stem cells  pluripotent stem cells derived from somatic cells  a compelling alternative to allogenic cell  readily available from sources such as adult skin  can provide patient-specific cell-mediated therapy  Development of procedures to induce pluripotency of the somatic cells, without modification of the cellular genome
  • iPSC – Inducible Progenitor stem cells  standard methodology for induction of pluripotency in iPSC involves viral transduction using transcription factors including oncogenes  insertional mutagenesis and increased risk of tumor formation  Methodology for generation of iPSC is rapidly evolving, and reprogramming of adult somatic cells is now being demonstrated which avoids permanent transgene integration, using excisable plasmids.
  • CONCLUSION  Osteoarthritis is present in epidemic proportions in this country and around the world  Cell-based repair strategies are among the most promising of the available approaches  A critical barrier to success in cell-based articular cartilage repair is identification of a readily available exogenous source of cells with the ability to seamlessly repair articular cartilage damage and restore long-term joint function.  Yet… the future is out there in these tiny little invisible things…
  • We must welcome the Future, remembering that soon it will be the Past; we must respect the Past, remembering that once it was all that was humanly possible. Thanks !