Fundamental of mesenchymal stem cells as a promising candidate in regenerative medicine
1. Fundamental of Mesenchymal Stem
Cells as a promising candidate in
regenerative medicine
(The International Journal of Biochemistry & Cell Biology)
2.
3. 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
4. Figure 1. When an adult stem cell divides, one of the daughter cells goes on to create
specialized tissue cells.
10. 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.
11. 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.
12. 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
13. 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.
14.
15. 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)
16.
17. 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.
18. Acknowledgement
Chen, Y., Shao, J.Z., Xiang, L.X., Dong, X.J., Zhang,
G.R. 2008. Mesenchymal Stem Cells: A
promising candidate in regenerative medicine.
The International Journal of Biochemistry & Cell
Biology 40: 815-820.
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.
