cartilage repair using stem cell & orthobiologics
DESCRIPTION
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.TRANSCRIPT
Cartilage Regeneration: A challenge in OA KNEE
Dr Vaibhav Bagaria MBBS MS FCPS
Arthroplasty & Sports Surgeon: CARE hosp & ORIGYN, NagpurVisiting Arthroplasty Surgeon: Apollo Hospital, Noida &
Columbia Asia Hospital, GZB
A ‘Good Start’ Dr Jain ?
To recreate what God has created?
CAD 2012Mumbai,India
Cartilage regeneration In ‘Arthroplasty’ Meeting
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.
Cartilage
The challenge is to engineer cartilage that is biochemically, structurally and biomechanically similar to normal cartilage
• Bioactive factors• Extracellular matrix• Scaffold/delivery system• Mechanical stimulation• Genetic manipulation
Cells
Scaffold
Growth factor/peptide
Efficient cartilage repair
site/tissue specific cartilage
OA KNEECartilage 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
Since its introduction, ACI has become a widely applied surgical method with good to excellent clinical outcomes.
Attempts to regenerate articular cartilage have been introduce in clinical practice with autologous chondrocytes implantation (ACI)
Brittberg M et al (1994) N. Engl J Med
Cell expansion
> 70% cases of repair
intestinal
skin
blood
beta cell
mesenchymal
liver
retinal
neural
indefinite self renewal
differentiation
stem cellll
limited self renewal
progenitoritor cell
Stem cells
amniotic hES testicular
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
Stem Cells
Adult Mesenchymal stem cell based therapyMesenchymal 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 pro-chondrogenic signals such as TGF-β
Source of Stem Cell
Fat (AMSC) or Bone Marrow (BMSC) ?
www.abcam.com
mesenchymal stem cell
Bone marrow
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
ConcentrationSeeding
Arthroscopy
Adapted from Dr Khay-Yong SAW, KLSMC
Dri
lling
Dri
lling
Dri
lling
Dri
lling
Dri
lling
Dri
lling
Blood clot scaffold
References:
hESC- Human Embryonic Stem CellsLimitless 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! 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. Biomaterials 31:
6968-6980.
Gong G, Ferrari D, Dealy CN, Kosher RA (2010) Direct and
progressive differentiation of human embryonic stem cells into
the chondrogenic lineage. J Cell Physiol 224: 664-671.
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 cellsstandard 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.
CONCLUSIONOsteoarthritis 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 !