Fundamental of mesenchymal stem cells as a promising candidate in regenerative medicine

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  • Purple= trophectoderm (later form umbilical cord and placenta)Inner cell mass isolated
  • Remain Quiscent until they received the signal that trigger them to differentiate.Similar to embryonic cells, MSCs also can self-renew and differentiate but they do so with limited extend. Unlike embryonic stem cell, Adult stem cells don’t usually form cells outside their tissue type in vivo. (Research proof that this is possible)Regenerate damaged tissue due to injury to maintain the balance of homeostasis.What is self-renewal?
  • Sometimes the daughter cells that is destined to be specialized may itself divides one or more times, in which case we called it as progenitor cells. For instance, the myeloid cells may later differentiated into two different cells. This allow for a larger pool of specialized cells.
  • Endothelial = 内皮
  • MSCs are most often employed.
  • Easy to isolate and expended in vitro,
  • Figure shows the multilineage pathways of mesenchymal stem cells.
  • This suggested that MSCs are diversely distributed in vivo.MSCs from other sources shared many similar characteristics with bone marrow MSCs, but still showed some differences among each other in phenotype, proliferation and capacity of differentiation.
  • Plasticity is a basic for generating tissue for transplantation.MSCs are capable of undergoing unorthodox differentiation, giving rise to cells with visceral mesoderm, neuroectoderm and endoderm characteristics under specific experimental condition.
  • MSCs provide suitable hematopoietic microenvironment for self-renewal, proliferation and differentiation of hematopoietic stem cells.MSCs capable of differentiating into cells of most connective tissues in vitro once stimulated by certain cytokine, growth factors and chemicals.MSCs secrete soluble factors that alter the tissue microenvironment functionally outweighs their transdifferentiation ability in affecting tissue repair. For example, interleukin enhance regeneration ability of injured tissues, stimulate proliferation and differentiation of endogenous stem-like progenitors.
  • Xenogeneic environment = from individual belonging to different sp.MSCs have immunomodulatory properties by suppress many T cell, B cell and NK cell function and may also affect the activity of dendritic cells.Bone: cure osteogenesis inperfecta; cartilage: cartilage repair with the use of hyaluronan; myocardium: participate in cardiac repair by differentiate into cardiomyocyte and vascular endothelial cells, also secrete various anti-apoptotic factors; Fat: generate adipose tissue for soft tissue reconstruction. Bag of fat are more suitable for some plastic surgery rather than saline bag or silicon.

Transcript

  • 1. Fundamental of Mesenchymal Stem Cells as a promising candidate in regenerative medicine(The International Journal of Biochemistry & Cell Biology)
  • 2. Adult Stem Cells• Undifferentiated cells• Found throughout the body after embryonic development• Multipotent• Capable of self-renewal and differentiation with limited extend• Regenerate damaged tissue
  • 3. Figure 1. When an adult stem cell divides, one of the daughter cells goes on to createspecialized tissue cells.
  • 4. Type of Adult Stem Cells• Hematopoietic • Endothelial• Mammary • Olfactory• Mesenchymal • Neural Crest• Neural • Testicular
  • 5. Mesenchymal Stem Cells (MSCs)• Marrow stromal cells• Multipotent stromal cells• Mesenchymal stromal cells• Colony-forming unit fibroblast (CFU-Fs)• Bone marrow stromal stem cells• Stromal Precursor cells• Skeletal stem cells• Multipotent adult progenitor cells
  • 6. Properties• Fibroblast-like colonies• Readily adhere on the culture surface• Capable of differentiating into Osteogenic Adipogenic Chondrogenic
  • 7. Hematopoietic and stromal cell differentiation
  • 8. Cells origin• Bone marrow is the richest and most reliable reservoir for MSCs.• Also found in adipose tissue, synovial membrane, skeletal muscle, dermis, pericytes, trabecular bone, umbilical cord, lung, dental pulp, amniotic fluid, fetal liver and peripheral blood.
  • 9. Plasticity• Differentiate into cell types in organs /tissues other than those expected from the cells predicted lineage.• MSCs could engraft in bone, muscle, brain, lung, heart, liver, gastroin testinal tract and hematopoietic system when transplanted.• Plasticity nature of MSCs remain arguable due to lack of experiment reproducibility.
  • 10. Functions• MSCs in bone marrow contribute to the formation of HSC “niche”.• MSCs serve as precursors of bone, cartilage and adipocytes.• MSCs shows a strong tendency to repair tissue damage in response to injury and disease. – Secrete soluble factors
  • 11. Associated pathologies• MSCs are immunological immature, thus able to survive in a xenogeneic environment.• Autologous MSCs are free from immune rejection and carcinogenesis and also circumvent ethical constraints.• MSCs may be useful in the repair or generation of damaged or mutated tissue including bone, cartilage, myocardium, fat, brain and liver.
  • 12. Cont.• MSCs selectively migrate to areas of injury/ inflammation and tumors.• SDF-1/CXCR4 was suggested to play important role in MSCs migration toward injury site.• Capable of inhibiting immune responses in a major histocompatibility complex- independent manner. – Acute graft-versus-host disease (GVHD)
  • 13. Summary• Mesenchymal Stem Cells – Reside in the connective tissue of most organs. – Can differentiate into multiple mesenchymal lineages: cartilage, bone and adipose tissues. – Possess the capacity to transdifferentiate. – Can migrate to sites of injury, inflammation and tumor. – Can alter tissue microenvironment via secretion of soluble factors.
  • 14. AcknowledgementChen, Y., Shao, J.Z., Xiang, L.X., Dong, X.J., Zhang,G.R. 2008. Mesenchymal Stem Cells: Apromising candidate in regenerative medicine.The International Journal of Biochemistry & CellBiology 40: 815-820.
  • 15. Thank you very much!