The Stem Cell in Orthopaedic surgery.pptx

The Stem Cell in Orthopaedic surgery

1. Stem Cell and Tissue Renewal Supervisor: Prof. Dr. dr. Ismail Hadisoebroto Dilogo , SpOT (K) Presentan Aslambotilangih

2. Stem Cell / Sel Punca unspecialized self renewal can be induced to form specific cell types

3. 1 stem cell Self renewal - maintains the stem cell pool 4 specialized cells Differentiation replaces dead or damaged cells throught the life Why self-renew AND differentiate? 1 stem cell

4. Properties of stem cell Clonogenic , a single ES cell gives rise to a colony of genetically identical cells, which have the same properties as the original cell Expresses the transcription factor Oct-4 Can be induced to continue proliferating or to differentiate Lacks the G1 checkpoint in the cell cycle ES cells spend most of their life cycle in S phase Don’t show X inactivation

5. Types of Stem Cells based on potential Stem cell t y pe D esc ri p t i o n Examp l e s T o t i p o t ent Each cell can develop into a new individual Pluripotent Pluripotent Cells can form any (over 200) cell types Multipotent Cells differentiated, but can form a number of other tissues Cells from early (1-3 days) embryos Some cells of blastocyst (5 to 14 days) Fetal tissue, cord blood, and adult stem cells

6. Types of Stem Cell

7. Embryonal stem cells Derived from the blastocyst, which is made up of an outer layer of cells (the trophectoderm), a fluid ectoderm filled cavity (the blastocoele ), and a cluster of cells on the interior. The ICM, which contains the ES cells must first be isolated from the surrounding trophoblast cells Capable of self-renewal and differentiation into cells of all tissue lineages, and they have the capacity for exceptionally prolonged culture (1–2 years with cell division every 36–48 hours) ES cells are difficult to derive and maintain in culture

8. Adult Stem Cells (Somatic Stem Cell): Definition: Undifferentiated cells found living within specific differentiated tissues in our bodies that can renew themselves or generate new cells that can replenish dead or damaged tissue Types of Adult Stem Cells: Hematopoietic Stem Cells (Blood Stem Cells) Mesenchymal Stem Cells Neural Stem Cells Epithelial Stem Cells Skin Stem Cells Fortier LA. Stem cells : Classifications, controversies , and clinical applications. Vet Surg . 2005;34(5):415–23.

9. Sources of Stem Cells

10. Mechanism of Action Inefficient Differentiation and Regeneration of Implanted Cells Secretion of Paracrine Factors

11. The Paracrine Effect MSCs secret a wide spectrum of paracrine factors that exert different functions on its vicinity. In the form of vesicles, cytokines, growth factors, etc Microenvironment dependent ( Eg. stress-induced, molecular stimulated) Source-dependent

12. MSC Mesenchymal stem cells (MSCs) are fibroblast-like multipotent adult stem cells derived from multiple tissue (including bone marrow, adipose tissue, umbilical cord, and dental pulp) with the capacity to self-renew. MSC characterization was proposed by the International Society for Cellular Therapy (ISCT) to aide in cell culture consistency be plastic adherent when kept under standard culture conditions express the proper positive and negative MSC markers and retain a multipotent phenotype with the ability to differentiate into adipocytes, osteoblasts and chondrocytes under the standard differentiation conditions.

13. One of the main advantages of MSCs is their immunomodulatory properties. Andrzejewska A, Lukomska B, Janowski M. Concise Review: Mesenchymal Stem Cells: From Roots to Boost. Vol. 37, Stem Cells. 2019. p. 855–64.

14. Andrzejewska A, Lukomska B, Janowski M. Concise Review: Mesenchymal Stem Cells: From Roots to Boost. Vol. 37, Stem Cells. 2019. p. 855–64.

15. Andrzejewska A, Lukomska B, Janowski M. Concise Review: Mesenchymal Stem Cells: From Roots to Boost. Vol. 37, Stem Cells. 2019. p. 855–64.

16. Allogenic MSC: Safety Profile Poor expression of Human Leukocyte Antigen (HLA-II) Undifferentiated & differentiated MSC do not elicit alloreactive lymphocyte proliferative responses & modulate immune responses. MSC hypoimmunogenic & suppress T cell alloproliferation in mixed lymphocyte reactions.

17. Allogenic MSC: Safety Profile Deans RJ, Moseley AB. Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol 2000;28:875-84. Le Blanck K et al. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol . 2003; 31(10):890-6 Montespan F et al. O Osteodifferentiated Mesenchymal Stem Cells from Bone Marrow and Adipose Tissue Express HLA-G and Display Immunomodulatory Properties in HLA-Mismatched Settings: Implications in Bone Repair Therapy. J of Immun Research 2014:230346 Ryan JM et al. Mesenchymal stem cells avoid allogeneic rejection. J Inflamm 2005,2:8

18. Tissue Engineering Triad Scaffold Signalling molecules Cells Improvement Time Appropriate environment Hydroxyapatite Osteogenic cells BMP Mechanical stability, infection control Fracture healing

19. Tissue Engineering Triad 1. A scaffold that provides structure and substrate for tissue growth and development 2. A source of cells to facilitate required tissue formation 3. Growth factors or biophysical stimuli to direct the growth and differentiation of cells within the scaffold However, not only are these components individually important, understanding their interactions is key for successful tissue engineering Murphy CM, O’Brien FJ, Little DG, Schindeler A. Cell-scaffold interactions in the bone tissue engineering triad. Vol. 26, European Cells and Materials. 2013. p. 120–32.

20. Components of the Tissue Engineering Triad

21. Principal cell therapeutic strategies for treating diseased or injured tissues (1) implanting isolated cells whole cell populations can be directly transplanted or isolated cells can be cultured and expanded ex vivo prior to re-implantation (2) implanting a construct assembled from cells and scaffolds deliver a combination of whole cell isolates or ex vivo cultured cells seeded onto a substrate template (3) in situ tissue regeneration by native cells In order to modulate the migration and tissue-appropriate differentiation of endogenous progenitors, drugs capable of affecting regulatory signals or proteins involved with the regulatory signalling cascade can be locally delivered For example, cells can be engineered to produce VEGF to stimulate angiogenesis or rhBMP-2 to promote osteoblastogenesis Murphy CM, O’Brien FJ, Little DG, Schindeler A. Cell-scaffold interactions in the bone tissue engineering triad. Vol. 26, European Cells and Materials. 2013. p. 120–32.

22. 1. Pore size, pore interconnectivity, and total porosity are essential considerations in scaffold development 2. Optimal pore size varies depending on the biomaterials used and application of the construct 3. Cells travelling through larger pores may migrate slower, but their directional movement allow them to travel further into the scaffold. 4. Larger pore size can overcome the advantages of specific surface area by increased cell migration and scaffold infiltration Murphy CM, O’Brien FJ, Little DG, Schindeler A. Cell-scaffold interactions in the bone tissue engineering triad. Vol. 26, European Cells and Materials. 2013. p. 120–32.

23. UC-MSC for Fracture Non-Union Patients diagnosed with fracture non-union are treated with UC-MSC based on the diamond concept / tissue engineering Routine follow up for x-ray and functional asssessment

24. Research on Stem Cell: Statistics

25. Research on MSC

26. Research Topics on MSC

27. Stem Cell: Potential Uses

28. Ongoing Stem Cell Research in RSCM Knee osteoarthritis Fracture non-union Fracture non-union with bone defect Spinal cord injuries Tuberculous spondylitis Diabetes mellitus Glaucoma Burn injury Erectile dysfunction Stroke Cerebral palsy

29. MSC for Osteoarthritis Intraarticular injection of UC-MSC for patients with knee osteoarthritis UC-MSC given once, followed with intraarticular injection of hyaluronic acid Routine follow up using questionnaire, x-ray, and MRI T2 map

30. Comparison with Other Studies In this study, we also noted that the greatest improvement of knee function was observed after 6 months of follow-up. This finding is in line with previous studies, which found that the maximum results were achieved at 6 months of follow-up but decline afterwards. Centeno, in May 2008, administered MSC in one subject with knee OA and obtained satisfactory result in the 6 th month. A trial by Emadedin in 2012 reported MSC transplantation in 6 patients with knee OA. The result was satisfactory on the 6 th month, but, slight decline was found on the 12 th month. However, the patients experienced improvement when compared to the baseline.

31. UC-MSC for Bone Defect

32. UC-MSC for Spinal Cord Injuries Implantation of UC-MSC in cases of spinal cord injuries are giving promising results

33. OBSTACLES TO CLINICAL APPLICATIONS Immunorejection by Recipient One of the commonly cited advantages of the use of MSCs compared to ES cells is the use of autogenous cells, and therefore avoidance of immune rejection by the recipient. Allogenous MSCs appear to be immunoprivileged and could provide a readily available source of MSCs, but they would also carry the risks of disease transmission from donor to recipient Engraftment The issue of localization of stem cells to injured tissues becomes important when considering the application of stem cell therapy to areas or tissues not amenable to direct injection One of the fundamental questions regarding stem cell engraftment is the importance of the actual number or percentage of donor stem cells in the recipient tissue.

34. Conclusion Stem cell treatment yields promising results in various cases We still have a long way to go; research on stem cell is still developing

35. Thank you