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MESENCHYMAL
STEMCELLS
Sharmila.C
18UT18
Introduction
Mesenchymal stem cells [MSCs] also known as
mesenchymal stromal cells or medicinal signaling cells.
Initially , in 1991 , the term referred to cells from bone
marrow.
They are multipotent stromal cells that can
differentiate into a variety of cell types , including
osteoblasts (bone cells) , chondrocytes (cartilage cells) ,
myocytes (muscle cells ) and adipocytes (fat cells) .
In Latin it is Cellula mesenchymatica praecursoria
History
• In 1924, Russian born morphologistAlexander A. Maximov used extensive histological findings to
identify a singular type of precursor cell within mesenchyme that develops into different types of
blood cells.
• Scientists Ernest A. McCulloch and James E.Till first revealed the clonal nature of marrow cells in the
1960s.
• The first clinical trails of MSCs were completed in 1995 when a group of 15 patients were injected with
cultured MSCs to test the safety of the treatment. 200 clinical trials have been started.
• Culturing marrow stromal cells in the presence of osteogenic stimuli such as ascorbic acid, inorganic
phosphate and dexamethasone could promote their differentiation into osteoblasts.
• In contrast, the addition of transforming growth factor – beta could induce chondrogenic markers.
Morphological Structure
Mesenchymal stem cells are characterized
morphologically by a stem cell body with a few cell
processes that are long and thin.
The cell body contains a large, round nucleus with a
prominent nucleolus , which is surrounded by finely
dispersed chromatin particles, giving the nucleus a clear
appearance.
The remainder of the cell body contains a small amount of
golgi apparatus, rough endoplasmic reticulum,
mitochondria and polyribosomes.
The cells which are long and thin, are widely dispersed and
the adjacent extracellular matrix is populated by a few
reticular fibrils but is devoid of the other types of collagen
fibrils.
These distinctive morphological features of mesenchymal
stem cells can be visualized label free using live cell
imaging.
Location
 Bone marrow
 Cord cells
 Molar cells
 Amniotic fluid
Bone marrow
Bone marrow was the original source of MSCs and still
is the most frequently utilized.
These bone marrow stem cells do not contribute to the
formation of blood cells and so do not express the
hematopoietic stem cell marker CD34.
They are sometimes referred to as bone marrow
stromal stem cells
Function
• Differentiation capacity
• Immunomodulatory effects
• Antimicrobial properties
• Differentiation capacity
MSCs have a great capacity for self renewal while maintaining
their multipotency.
The degree to which the culture will differentiate varies among
individuals and how differentiation is induced, e.g., chemical
vs mechanical
The capacity of cells to proliferate and differentiate is known to
decrease with the age of the donor , as well as the time in
culture.
Cont..
• Immunomodulatory effects
MSCs have an effect on innate and specific immune cells .
MSCs produce many immunomodulatory molecules including prostaglandin E2 (PGE2),
nitirc oxide, indoleamine 2,3 – dioxygenase , interleukin 6 and other surface markers such as
fast PD – L1 and PD – L2.
MSCs are able to migrate to the site of injury where they polarize through PGE2 macrophages
in M2 phenotype which is characterized by an anti – inflammatory effect.
• Antimicrobial properties
MSCs produce several antimicrobial peptides including human
cathelicidin LL – 37, β – defensins, lipocalin.
These peptides together with the enzyme indoleamine 2,3
dioxygenase are responsible for the broad spectrum
antibacterial activity of MSCs.
Clinical significance
• Autoimmune Disease -> treating disease are in preliminary development
understanding autoimmune disease , chron’s disease , multiple sclerosis , systematic lupus
erythematosus and systemic sclerosis.
• Other disease -> many of the early clinical successes using intravenous transplantation came in
systemic disease such as graft versus host disease and sepsis.
• Detection -> a cell can be classified as an MSC if it shows plastic adherent properties under
normal culture conditions and has a fibroblasts like morphology. In fact , some argue that MSCs and
fibroblasts are functionally identical..
Mesenchymal stemcells

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Mesenchymal stemcells

  • 2. Introduction Mesenchymal stem cells [MSCs] also known as mesenchymal stromal cells or medicinal signaling cells. Initially , in 1991 , the term referred to cells from bone marrow. They are multipotent stromal cells that can differentiate into a variety of cell types , including osteoblasts (bone cells) , chondrocytes (cartilage cells) , myocytes (muscle cells ) and adipocytes (fat cells) . In Latin it is Cellula mesenchymatica praecursoria
  • 3. History • In 1924, Russian born morphologistAlexander A. Maximov used extensive histological findings to identify a singular type of precursor cell within mesenchyme that develops into different types of blood cells. • Scientists Ernest A. McCulloch and James E.Till first revealed the clonal nature of marrow cells in the 1960s. • The first clinical trails of MSCs were completed in 1995 when a group of 15 patients were injected with cultured MSCs to test the safety of the treatment. 200 clinical trials have been started. • Culturing marrow stromal cells in the presence of osteogenic stimuli such as ascorbic acid, inorganic phosphate and dexamethasone could promote their differentiation into osteoblasts. • In contrast, the addition of transforming growth factor – beta could induce chondrogenic markers.
  • 4. Morphological Structure Mesenchymal stem cells are characterized morphologically by a stem cell body with a few cell processes that are long and thin. The cell body contains a large, round nucleus with a prominent nucleolus , which is surrounded by finely dispersed chromatin particles, giving the nucleus a clear appearance. The remainder of the cell body contains a small amount of golgi apparatus, rough endoplasmic reticulum, mitochondria and polyribosomes. The cells which are long and thin, are widely dispersed and the adjacent extracellular matrix is populated by a few reticular fibrils but is devoid of the other types of collagen fibrils. These distinctive morphological features of mesenchymal stem cells can be visualized label free using live cell imaging.
  • 5. Location  Bone marrow  Cord cells  Molar cells  Amniotic fluid Bone marrow Bone marrow was the original source of MSCs and still is the most frequently utilized. These bone marrow stem cells do not contribute to the formation of blood cells and so do not express the hematopoietic stem cell marker CD34. They are sometimes referred to as bone marrow stromal stem cells
  • 6. Function • Differentiation capacity • Immunomodulatory effects • Antimicrobial properties • Differentiation capacity MSCs have a great capacity for self renewal while maintaining their multipotency. The degree to which the culture will differentiate varies among individuals and how differentiation is induced, e.g., chemical vs mechanical The capacity of cells to proliferate and differentiate is known to decrease with the age of the donor , as well as the time in culture.
  • 7. Cont.. • Immunomodulatory effects MSCs have an effect on innate and specific immune cells . MSCs produce many immunomodulatory molecules including prostaglandin E2 (PGE2), nitirc oxide, indoleamine 2,3 – dioxygenase , interleukin 6 and other surface markers such as fast PD – L1 and PD – L2. MSCs are able to migrate to the site of injury where they polarize through PGE2 macrophages in M2 phenotype which is characterized by an anti – inflammatory effect. • Antimicrobial properties MSCs produce several antimicrobial peptides including human cathelicidin LL – 37, β – defensins, lipocalin. These peptides together with the enzyme indoleamine 2,3 dioxygenase are responsible for the broad spectrum antibacterial activity of MSCs.
  • 8. Clinical significance • Autoimmune Disease -> treating disease are in preliminary development understanding autoimmune disease , chron’s disease , multiple sclerosis , systematic lupus erythematosus and systemic sclerosis. • Other disease -> many of the early clinical successes using intravenous transplantation came in systemic disease such as graft versus host disease and sepsis. • Detection -> a cell can be classified as an MSC if it shows plastic adherent properties under normal culture conditions and has a fibroblasts like morphology. In fact , some argue that MSCs and fibroblasts are functionally identical..