JOURNAL READING

Mesenchymal Stem Cells for

Cartilage Repair in Osteoarthritis

Oleh:
Edina Theodora A. Sagala (I11110007)
Khalik Perdana Putra (I11110027)
Qory Irsan (I11110028)
Vidia Asriyanti (I11110031)

KEPANITERAAN KLINIK ILMU BEDAH

RS BHAYANGKARA ANTON SOEDJARWO
FAKULTAS KEDOKTERAN UNIVERSITAS TANJUNGPURA
 Abstract
Osteoarthritis (OA) degenerative disease of connective
tissue and progress with age or develops in young athletes
following sports-related injury
The articular cartilage vulnerable to damage and poor
potential for regeneration
Currently available treatment surgical and pharmaceutical
restoration of normal cartilage function difficult.
Bone marrow stromal cells (BMSCs) or bone marrow-derived
mesenchymal stem cells has chondrogenic differentiation
potential ideally suited for therapeutic use in cartilage
regeneration.
BMSCs potential to modulate local microenvironment, protect
cartilage from further tissue destruction, and facilitate
regeneration of the remaining progenitor cells in situ.
 Introduction
Normal joint movements depend on
normal anatomical structures of the
tissue (joint cartilage and synovial
membrane) helps perfoming
physiological functions
 The cartilage components predominantly
extracellular matrix (ECM) and an aggregate-
forming proteoglycan, aggrecan, with
embedded chondrocytes
The ECM dense framework collagen fibers of
mainly type II with small amounts of other
subtypes of collagen.
This unique biomechanical and structural
composition of cartilage enables the tissue to
balance its mechanical sturdiness and
flexibility.
 Osteoarthritis (OA) has direct effect
on function of several joints knee
is the most clinically important.
Estimated that all individuals above
age 65 have some clinical or
radiographic evidence of OA.
Pathogenesis of
Osteoarthritis
 Current Treatment for
Osteoarthritis
Mild cases of OA combination non-pharmacologic
(e.g. physiotherapy) and pharmacologic agents to
reduce pain and inflammation
Disease progress additional aggressive
treatments intra-articular steroids (Hycort) or
hyaluronic acid (Hyalgan) administration
Advanced or severe cases knee replacement
Suggested reverse OA pathophysiology
application cell-based therapies used cultured
autologous chondrocytes for cartilage regeneration
has been used successfully for over a decade
 Mesenchymal Stem Cells and
Chrondogenesis
BMSCs differentiate in the presence of
appropriate growth stimuli along spesific
pathways for producing cartilage tissue
Mesenchymal stem cells (MSCs) isolated first
from bone marrow and subsequently from
variety of other tissue such as adipose tissue,
placenta, umbilical cord and cord blood,
dental pulp, and amnion
MSCs or MSClike cells are believed to
replace cells lost due to aging or tissue injury
 MSC has no spesific marker, International Society
of Cell Therapy defined these cells to be positive
for stromal cell markers CD73, CD105, and CD90
and negative for hematopoietic markers.
BMSCs have self-renewing ability and
differentiation potential into chondrocytes,
adipocytes, and osteocytes
Chondrogenic differentiation of BMSCs is a
complex interactive network between
transcriptional factors, extracellular growth
factors, and signal transduction pathways.
 The intrinsic chondrogenic differentiation potential
of BMSCs controlled by transcription factors sox-9
and runx-2 whereas Transforming Growth Factor
(TGF) and bone morphogenetic protein
Parathyroid hormone like peptide and basic
fibroblast growth factor regulating terminal
differentiation of BMSCs by suppressing collagen X
and maintaining expression other matrix protein
prevent hypertrophic differentiation
Bone marrow-derived MSCs can be used as a
cell source for cartilage repair
 MSCs isolated from bone marrow and adipose
tissue loaded on three-dimensional scaffold
under appropriate differentiation cues
acquire chodrogenic phenotype resulting
construct used as replacement tissue for
cartilage repair.
Quality of cartilage produced by using bone
marrow-derived stromal cells is substantially
lower than obtained by using chodrocytes.
Researcher combine BMSCs with several
biomaterial to improve scaffolds.
 Biology of Mesenchymal Stem
Cells
BMCs are known to preferentially home and
accumulate to the site of injury an
inflammation.
The SDF1/CXCR pathway is a key regulator for
BMSC migration, and in the absence of SDF1
signal, migration of these cells to the bone
tissue has been found to be impaired.
These cells are also known to secrete a large
number of growth factors, cytokines, and
chemokines that carry out different functions.
 Paracrine activity MSCs mediate
anti-inflammatory, anti-
apoptotic, anti-fibrotic,
angiogenic, mitogenic, and
wound healing.
The biological mediators secreted by
MSCs has been shown to be
important in regulating regeneration
of variety damage organs of the
body.
Immunomodulatory Properties of
Mesenchymal Stem Cells (MSC)
Hypoimmunogenic
MSCs express low to intermediate
level of HLA class I antigens and
negative HLA class II molecules
Posses immunosuppresive activity
Negative costimulatory molecules for
alloreactive T cell stimulation
 Pre-clinical Efficacy of MSC in
Cartilage Regeneration
MSC transplantation effective for cartilage
repair in various preclinical models of OA
Autologous BMSCs injected intra-articular
in goats which OA induced by surgery
found regeneration of tissues
Undifferentiated and predifferentiated
BMSCs on scaffold have potential to be
therapeutically effective for degenerative
disease in rabbit, sheep, and models of OA.
Bone Marrow Stromal Cell-Based
Therapy for Cartilage Repair
Complete defect fill with
fibrocartilagionus tissue
Improvement in cartilage
regeneration
Reduction in pain : low dose (50
million cells) and high dose (150
million dose)
Improvement physical function
Significant improvement in
quality of live
 Conclusion
BMSCs have some characteristics that used for
cartilage repair :
- Migrate and engraft onto multiple
musculoskeletal tissues, especially at the
site of injury undergo tissue-specific
differentiation.
- Anti-inflammatory and immunosuppressive
properties for allogeneic transplantation
- Induce proliferation and differentiation of
resident progenitor cells or their innate
differentiation potential to chondrocytes
aid regeneration of the damaged cartilage
- Combination of paracrine activity and
differentiation ability may be operative in
 The exact mechanism by which
BMSCs are expected to regenerate
articular cartilage in patients with OA
is not clear
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