Different treatments of osteochondral defect repair either traditional surgical procedures or cell therapeutics.

1. Treatment of Osteochondral Defects:
Past, Present and Future.
Dr./ Elhussein Elbadry Mahmoud
Lecturer of animal surgery, SVU, Egypt.
Postdoc Fellow, Stanford University, USA.

2.  The complexity of osteochondral lesions remains a great
challenge for clinicians and researchers due to the demand
for cartilage, bone, and bone-cartilage interface repair.
Cartilage
Bone-cartilage
interface
Subchondral bone
 Osteochondral defects include damage to both the articular
cartilage as well as the underlying subchondral bone.

3. Treatment strategies of osteochondral lesions
 Reparative surgical techniques.
 Cell therapeutics.

4. Reparative surgical techniques
Subchondral drilling.
Microfracture.
osteochondral graft.
Drawbacks of theses techniques:
 Inferior fibrous tissue repair.
 Subchondral cysts.
 poor integration with surrounding tissue.
 long-term deterioration of the repaired tissue.

5. Cell therapeutics
1- Autologous chondrocyte implantation (ACI)
In 1994, ACI started as the first promising cell-based therapy option for addressing cartilage defects.

6. Restrictions of ACI
Not suitable for osteochondral and large defects.
Dedifferentiation of chondrocytes.
Donor site morbidity.
Required additional surgery.
Wide spread of the chondrocytes in the whole knee joint post-injection. For
this, Matrix autologous chondrocyte implant (MACI) was fabricated which
localizes the chondrocytes in the defect site, but it needs open surgery.

7. 2- Mesenchymal Stem Cells (MSCs)
Cell therapeutics
• Self renewal.
• Pluripotency.
• Easy accessibility from different sources.
• Safe.

8. Fibroblastic-like cells (MSCs).

9. MSCs properties are variable according to source.

10. MSCs Delivery
Although intra-articular injection of MSCs is the most convenient minimal invasive
treatment method for repair of osteochondral defects, the results are unsatisfactory.
So, delivery of MSCs into the defect site plays a pivotal role for success of their applications.

11. Most of the established studies used natural or synthetic materials acts as scaffold
for delivery MSCs into the determined area.
(Nöth et al. Advanced Drug Delivery Reviews, 2010).

12. Experimental and clinical studies used different scaffolds for maintaining
MSCs into the defect area, but there was no significant difference
between MSCs + scaffold and MSCs alone. This suggested due to
harmful biodegradation by-products of scaffold on MSCs.

13. A new delivery system named cell magnetic system was established.
Bone marrow MSCs were magnetically labeled using ferucarbotran (Resovist), and named
magnetic mesenchymal stem cells (m-MSCs), which transplanted into the osteochondral defect
at weight bearing portion of the medial femoral condyle, with aid of an external magnetic device
for localization of the MSCs into the defect area.

14. Transplantation of m-MSCs into osteochondral defect of the
medial femoral condyle with exposure to magnetic device.
Experimental animal studies reported that m-MSCs improved complete regeneration
of the subchondral bone covered by layer of hyaline cartilage and confirmed by
collagen type II.

15. Orthopaedic group at Hiroshima University got governmental permission
for using autologous m-MSCs in 5 patients to check safety and efficacy of
autologous m-MSCs for cartilage defects.
https://www.youtube.com/watch?v=izk-6acVEaU
This study represented complete coverage of the cartilage defects with
hyaline cartilage with long-term follow-up 48 weeks.

16. (Kamei et al. KSSTA, 2018).

17. Limitations of using autologous MSCs
 Age.
 Invasiveness.
 Time.
(Caplan A. J Cell Physiol, 2007).

18. MSCs might be potentially immune-privileged
 Inhibition of T-cell proliferation.
 Breakdown of T-cell division.
 Modulation of the inflammatory cytokines.
(Aggrewal S, Pittenger M. Blood, 2005).
As well, using of allogeneic MSCs is
alternative source for autologous one.
In addition, absence of surface markers and
co-stimulatory factors of MSCs. So, Immune
system can not identify MSCs.

19. Recent study was to investigate the safety and usefulness of using allogeneic
magnetically labeled mesenchymal stem cells (m-MSCs) to ameliorate
osteochondral repair as alternative source to autologous one, with immune
surveillance using mixed lymphocyte reaction (MLR) assay. This study showed no
histological difference between autologous and allogeneic m-MSCs.
Allogeneic m-MSCs are a safe alternative source to autologous m-MSCs, upholding
repair of an osteochondral defect for clinical application using universal donor
MSCs through a one-stage surgical procedure.

20. Sources of universal allogeneic MSCs
Cell type Product name Sponsor Country
BMSCs Prochymal OSIRIS Therapeutic USA
BMSCs CardioCell STEMEDICA USA
UC-MSCs Cartistem Medipost Korea

21. Thank You