challenge in OA
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 ?
To recreate what God has created?
Cartilage regeneration In ‘Arthroplasty’ Meeting
Cartilage consists of cells called chondrocytes and
extensive extracellular matrix rich in
glycoaminoglycans, proteoglycans and
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
Efficient cartilage repair
site/tissue specific cartilage
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
Adult chondrocyte based
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
OATS -> ACI -> MACI -> HACI (hyaluronan
scaffold) -> CCI ( characterized by
Cartilage repair FIRST GEN
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
> 70% cases of repair
Since its introduction, ACI has become a widely applied surgical
method with good to excellent clinical outcomes.
Adult Mesenchymal stem
cell based therapy
Mesenchymal Stem Cells (MSC) can be
obtained from bone marrow, synovium, fat, or
Distinct potential for differentiation into the
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  which may release prochondrogenic signals such as TGF-β
Source of Stem Cell
Fat (AMSC) or Bone Marrow (BMSC) ?
Principles of Chondrogenesis
Depth 5 to 10mm
1 to 2mm gaps
Light burring in
between drill holes
AMSC + Matrix
hESC- Human Embryonic
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
Safety: ? Teratoma, Xenogenic contamination,
Immune rejection( caritlage immune privileged
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
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
Development of procedures to induce
pluripotency of the somatic cells, without
modification of the cellular genome
iPSC – Inducible Progenitor
standard methodology for induction of
pluripotency in iPSC involves viral transduction
using transcription factors including oncogenes
insertional mutagenesis and increased risk of
Methodology for generation of iPSC is rapidly
evolving, and reprogramming of adult somatic
cells is now being demonstrated which avoids
permanent transgene integration, using
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
We must welcome the Future,
that soon it will be the Past;
we must respect the Past,
remembering that once it was
all that was humanly possible.