Different treatment options for knee osteoarthritis in 2019

1. Knee Osteoarthritis Treatment in 2019
Dr./ Elhussein Elbadry Mahmoud
Lecturer of animal surgery, SVU, Egypt.
Postdoc Fellow, Stanford University, USA.

2. Joint
It is a complex organ connect between two or more bones and it is
critical for athletic performance.
Functions:
 To allow smooth and as frictionless as possible motion of the bony ends.
 Stability of musculoskeletal system.
 Restriction of the motion in unwanted directions.

3.  Structure of knee Joint.
 Hyaline cartilage.
- Cellular component: Chondrocytes
- Extracellular matrix: Mainly water (70-80%), collagen, proteoglycans
 Joint capsule (inner vascular and outer fibrous layers).
 Synovial fluid (Lubrication and nutrition).
 Ligaments.

4.  Osteoarthritis (OA) is defined as a disease of joints characterized
by the deterioration of articular cartilage and exposure of the
subchondral bone, leading to pain and loss of mobility.

5. OA-associated knee lesions involve femoral and tibial articular cartilage, and
subchondral bone as well as those of meniscal, ligamentous and synovial tissues.

6. Stages of OA
Mild OA.
Moderate OA.
Severe OA.

7. 1. Osteophytes (circled).
2. Asymmetric joint space narrowing (short arrow).
3. Subchondral sclerosis (long arrow).
OA
radiological
lesions.

8.  Real cause of OA is still unknown.
 Several predisposing factors were recorded such as age, sex, pre-
existing joint deformity, obesity, genetic factors, and trauma.

9. The levels of proinflammatory cytokines, including IL-1β, TNF and IL-6, are elevated in OA. These cytokines
contribute to the pathogenesis of OA through several mechanisms including downregulation of anabolic events and
upregulation of catabolic and inflammatory responses, effects that result in structural damage to the OA joint.
Abbreviations: ADAMTS, a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs; IL, interleukin;
MMP, matrix metalloproteinase; OA, osteoarthritis; TNF, tumor necrosis factor.
Role of proinflammatory cytokines in the pathophysiology of osteoarthritis

10. Treatment Strategies
 Palliative Treatment.
 Surgical Correction.
 Regenerative Therapy.

11. Palliative Treatment
 Intra-articular injections of corticosteroids.
 Intra-articular injections of hyaluronic acid (HA).
Toxic for chondrocytes and lead to OA
progression with long-term administration.
Controversial results

12. Surgical Correction
High tibial osteotomy (HTO):
To decrease compressive load on the affected compartment.
Total Knee replacement (TKR): in case of late stage of OA.
TKR HTO

13. Regenerative Therapy
 Cell-based therapy has been shown anabolic effect to reverse the pathological changes of OA.
 Endogenous mesenchymal stem cells (MSCs) in the synovial fluid play an important role in
chondrogenic differentiation, but with a limited number.
 So, It is preferable for using exogenous MSCs transplantation for improvement of the OA joint
environment.

14. Exogenous MSCs
Easy
accessibility
Anti-
inflammatory
Safe
Immune
privileged
Differentiation
Properties of MSCs
Bone marrow
Synovium
Synovial fluid
Adipose tissue
Umbilical cord
Muscle
Periosteum
Chondrocytes
Osteoblasts
Adipocytes
Large number of
growth factors
Non-tumorgenic
except iPS and ES
cells
Inhibition of T-cell
proliferation.
Breakdown of T-
cell division.

15. Many experimental studies used MSCs for OA treatment. Although, one of these
experimental studies reported that an intra-articular injection of MSCs reduce knee pain
but not prevent OA progression, there are many clinical trials for treatment of OA using
mesenchymal stem cells of different sources and different numbers.
https://clinicaltrials.gov/ct2/results?term=stem+cells&cond=Osteoarthritis&recrs=e&age_v=&gndr=&type=&rslt=&Search=Apply
Cell source Doses Phase Country
Autologous adipose stem cells Three doses (1,2,5 x 107) I & II China
Autologous bone marrow stem cells Two doses(1, 10 x 107) I & II Spain
Allogeneic bone marrow stem cells 4 x 107 I & II Spain
Autologous Adipose stem cells Three doses (1,5,10 x 107) I & II Korea
Autologous Adipose stem cells Three doses (2,10,50 x 106) I Germany
Allogeneic umbilical cord blood stem cells 2.5 x 106 cells/500㎕/㎠ II & III USA, Korea (Cartistem)
Autologous Adipose stem cells 1 x 108 II Korea (JointStem)

16. One crucial study reported that mesenchymal stem cells reduce pain but not
degenerative changes in a mono-iodoacetate rat model of osteoarthritis.
In 2019, New animal study has been demonstrated that multiple intra-articular
injections of allogeneic bone marrow stem cells are important to modulate OA
joint environment and restore the lost cells in all joint structures. While, single
injection of MSCs is not enough for OA treatment…
(Van Buul et al. J Orthop Res 2014.)
(Mahmoud et al. The bone & Joint Journal 2019)

17. Future hope
Generation of commercial stem cells product with a reasonable cost
ArthroStem®

18. Thank You