The document discusses the use of bone marrow stromal stem cells (bMSCs) therapy for musculoskeletal problems like discs, cartilage, and bone. It describes a study conducted in rabbits to evaluate the effectiveness of transplanting bMSCs and distracting the intervertebral disc to reverse disc degeneration. The study found that bMSCs transplantation combined with disc distraction led to improved disc height, higher proteoglycan content, and better histological scores compared to other treatment groups. The results suggest that bMSCs transplantation along with increasing disc rehydration through distraction can promote extracellular matrix repair and regeneration for intervertebral disc degeneration.

3. Disc and bone Cells matrix

4. Bone marrow stromal stem cells Skeletal stem cells (SSCs), also known as bone-marrow stromal stem cell, or mesenchymal stem cell

8. Tissue Engineering Triad

9. Core concept

16. Induction of MSCs to Osteoblast

18. Characterization of Osteoblasts

21. TISSUE ENGINEERING APPROACH TO BONE REPAIR BY AUTOLOGOUS BMSCs LOADED ON SUPPORT SCAFFOLDS

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23. Topic study cells scaffolds Bone Formation of Cultured Osteoblasts in Bone Defect of Radial Shaft of Rabbit Animal model (New Zealand white rabbits ) J. of Korean Orthop. Assoc. 2005; 40: 453-459 autologous cultured osteoblasts The effect of implants loaded with autologous mesenchymal stem cells on the healing of canine segmental bone defects. non-union defect in adult dog f e mor a J. Bone Joint Surg. Am.1998; 80, 985–996. Autologous MSC hydroxyapatite: beta-tricalcium phosphate (65:35) Autologous bone marrow stromal cells loaded onto porous hydroxyapatite ceramic accelerate bone repair in critical-size defects of sheep long bones. full-thickness gaps of tibia diaphysis in adult sheep J. Biomed. Mater. Res. 2000;49, 328–337. Autologous bone marrow stromal cells bioceramic composites Transplantation of marrow-derived mesenchymal stem cells and platelet-rich plasma during distraction osteogenesis—a preliminary result of three cases Clinical study achondroplasia patients bilaterally, and three femoral and one tibial lengthenings were done in four patients because of a limb length discrepancy, which was secondary to trauma (two limbs), congenital pseudarthrosis of the tibia (one), and developmental coxa vara (one) Bone 35 (2004) 892– 898 osteoblast-like cells platelet-rich plasma (PRP)

25. Topic study cells scaffolds Enhanced Tibial Osteotomy Healing with Use of Bone Grafts Supplemented with Platelet Gel or Platelet Gel and Bone Marrow Stromal Cells A prospective, randomized, controlled study . Thirty-three patients undergoing high tibial osteotomy to treat genu varum . J Bone J Surg.Br.2007 ; 11 Osteoblast Platelet gel

26. Topic study cells scaffolds Treatment of Osteonecrosis of the Femoral Head with Implantation of Autologous Bone-Marrow Cells prospective cohort study. T hirteen patients (eighteen hips) with stage-I or II osteonecrosis of the femoral head . J Bone J Surg.Am. 2004 autologous bone-marrow mononuclear cells

27. Study by Aziz Nather Department of orthopaedic surgery National University of Singapore

32. Conclusion 􀂄 Addition of MSCs improved the biological healing of the inert allografts. 􀂄 Addition of PRP did not have the same effect. 􀂄

36. Disc Cells matrix Water and proteoglycans increase from outer the annulus to the inner nucleus, and, in contrast, collagens are inversely distributed Collagen type I proteoglycans Nucleus pulposus chondrocyte-like cell Inner annulus Chondrocyte-like cells Outer annulus fibroblast or fibrocyte-like-cells End-plate chondrocyte Proteoglycans : aggrecans, versican, decorin, biglycan, fibromodulin, lumican, and perlecan. Collagen type II

41. M E T H O D S three sequential stages of experiments were designed :

43. Study on : 1. Developing of external compression and distraction device External compression device External distraction device Stage 2 : Interphase stage

45. 3. Establishing of method of isolation, culture, and preparation of transplantation of bone marrow stromal stem cells . Illiac crest bone marrow aspiration from rabbit donor Day 30 x 40

47. In vitro Study : Day 30 : bMSCs embedded in atelocollagen

49. kept alive for 8 weeks 24 new zealand white rabbits , average weight 3.34 kg Group 1 Group 2 Group 4 Group 3 External compression device, 2.3 MPa, loaded into L4-L5 for 14 days External compression device was removed 8 weeks unload sacrificed bMSCs transplantation Distract ion of the intervertebral disc bMSCs and IVD distraction

50. Tissue preparation : 22 days Lateral digital X-ray, Micro-CT scan -> disc height Macroscopic : morphological grade (Thomson, et al) Microscopic : histological score (Masuda and Boos,et al) and proteoglycans grade (Norcross, et al) Cell viability (Tunel reaction) and cell labeling (CFDA)

51. Surgical procedure

53. transplantation of 0.08 ml bMSCs solution are injected into disc by posterolateral approach and image intensifier guided through a 25-gauge syringe.

54. Image intensifier-guided

56. In vivo Cell labeling : 8 weeks after transplantation group 1 (bMSCs) group 4 (distraction and bMSCs)

57. RESULTS DISCUSSIONS

60. Group 3 Group 1 Group 2 Group 4

67. CONCLUSIONS

69. Cell Therapy and Stem cells for Cartilage Defect Courtesy of Dr. Andri Lubis, Sp OT Orthopaedic and Traumatology Division Faculty of Medicine University of Indonesia

71. cartilage MFC denuded 3x5 cm Osteochondral lesion

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80. Bone Marrow-Derived Mesenchymal Stem Cells

82. Courtesy of Prof. James Hui, National University Hospital, Singapore

85. Courtesy of Prof. James Hui, NUH

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87. Eur Radiol 2007; 17:103–18

89. Tissue Engineering and Cell Based Therapies: a 21 st Century Treatment Dr. Caplan

91. The End Thank you for the attention