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.

1. 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

2. A ‘Good Start’ Dr Jain ?
CAD 2012
Mumbai,
India
 To recreate what God has created?
 Cartilage regeneration In ‘Arthroplasty’ Meeting

3. 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.

4. 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

5. 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

6. Cellular based therapy
 Adult Chondrocyte
 Adult Mesenchymal Stem cell
 Human Embryonic Stem Cell
 Inducible Progenitor stem cell

7. 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)

8. 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.

9. 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

10. 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

11. 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

12. Source of Stem Cell
Fat (AMSC) or Bone Marrow (BMSC) ?

13. Bone marrow
mesenchymal
stem cell
www.abcam.com

14. 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

15. Technique
Bone Marrow
Aspiration
Concentration
Seeding

16. Arthroscopy

17. Adapted from Dr Khay-Yong SAW, KLSMC

20. Drilling
Drilling
Drilling
Drilling
Drilling
Drilling

21. Blood clot
scaffold

22. References:

23. 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.

24. 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

25. 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.

26. 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…

27. 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 !