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Mesenchymal Stem Cells (MSCs)

MSCs are multipotent stem cell which has the ability to self-renew and  differentiate.  It can differentiate into different kinds of cells and has a broad clinical application potential. MSCs can be found in the umbilical cord, dental pulp, fat and bone marrow.

Mechanism of Action

MSCs secrete bioactive factors and exosomes through endocrine/ paracrine system. Molecules of cytokines, growth factors, anti-oxidants and pro-angiogenic factors, and those that stimulate cell proliferation and angiogenesis are released. This decreases the response to stress and apoptosis of damaged cells. Tissues are repaired through regulation of local and systemic inflammatory and immune responses.

Unique Properties of Mesenchymal Stem Cells
  1. Homing function
    MSCs possesses homing function. When body tissue is stimulated, it will “wake” some “sleeping” MSCs and they will migrate to the site of injury. They will then differentiate and replace damaged cells. MSCs can regulate stem cell migration to targeted tissues through different signals, and repair damaged or aging tissues in the human body.
  2. Anti-inflammatory effect
    MSCs can reduce Graft-versus-host disease (GvHD) as they have innate immunogenic advantages. They can exert immune regulatory functions through direct contact and secretion of soluble cytoprotective factors to act on immune cells in the body and exert anti-inflammatory effects.
  3. Good secretion of cytokines
    MSCs have a strong ability to migrate, differentiate, and secrete a variety of good cytokines. These cytokines can stimulate MSCs to exert immunosuppressive functions and grow a large number of good stem cells in a short period of time to promote the survival of damaged cells.
  4. Promote angiogenesis
    Angiogenesis is carried out under the balance of various pro-angiogenic and anti-angiogenic factors. MSCs can induce and promote angiogenesis. Hence, it is known as the ideal cell for tissue regeneration. It has been used in the treatment of diseases such as skin defects, ischemic diseases, and nerve damage.
Potential Use of MSCs

MSCs have the ability to regulate the patient’s immune system. It promotes cell growth and also differentiates into various specialized cells. Its potential has been extended to a wide range of diseases such as heart disease, diabetes, Alzheimer’s disease, spinal cord injury, chronic trauma, Graft-versus-host disease, rheumatoid arthritis, liver cirrhosis, retinal diseases, and more.

MSCs Anti-Aging

Studies have shown that replenishing sufficient number of stem cells in the body can stimulate other stem cells found in the human body, which in turn improves metabolic functions of cells and organs. By this, aging as a whole can be delayed.

Its potential includes the following, such as boosting energy and physical strength, improving overall health, anti-aging, improving sexual desire, reconciling hormonal imbalance, firmer and fresher skin, and improving memory.

Why Umbilical Cord MSCs Are The Best?

Currently, MSCs derived from umbilical cord have greater application potential than mesenchymal stem cells derived from other tissues. It is the youngest and most primitive MSCs source available from the human body.

In addition, MSCs can be multiplied easily in the lab through cell culture, immunopriviledged, and also easy to obtain. MSCs also aid in HSCs transplant during engraftment.

Also, the umbilical cord’s Wharton Jelly contains the most abundant MSCs, as compared to other sources, such as bone marrow and umbilical cord blood.

Content Of Mesenchymal stem cells per 200 million [Nucleated cells]
Cord Blood1 cell
Adult Bone Marrow2,000 cells
Wharton’s Jelly666,000 cells

*Reference: BMC Cell Biology 2006,7: 14

Changes in Age and Content of MSCs

MSCs are “master” cells. As the human age increases, MSCs will gradually age and undergo apoptosis which causes a decline in total MSCs cell number and functionality, leading to skin aging.

Future Trends

Clinicaltrials.gov of the US National Institutes of Health (NIH) is the world’s largest clinical research database. According to the search results, as of October 18, 2019, there are 1002 registered MSCs clinical studies in the database, of which, China, Europe and the United States are among the world’s top three in clinical ranking.

From the perspective of the types of diseases treated, clinical research on mesenchymal stem cells involves hundreds of diseases. Nervous system, cardiovascular and orthopedic diseases are the three main research areas. In addition, diabetes, liver, lung, gastrointestinal tract, skin, and Graft-versus-host disease (GvHD) are also important clinical research directions for mesenchymal stem cells.

MSCs-Based Products Approved by Various Regulators (1)
No. Product name Company Approved country Regulator Year Indications Product Type
1 Queencell Anterogen Co. Ltd. South Korea MFDS (KFDA) 2010 Subcutaneous tissue defects Autologous human AT-MSC
2 Cellgram-AMI Pharmicell Co. Ltd. South Korea MFDS (KFDA) 2011 Acute myocardial infarction Autologous human BM-MSC
3 Cartistem Medipost Co. Ltd. South Korea MFDS (KFDA) 2012 Knee articular cartilage defects Allogeneic human UC-MSC
4 Cupistem Anterogen Co. Ltd. South Korea MFDS (KFDA) 2012 Crohn’s fistula Autologous human BM-MSC
5 Prochymal, remestemcel-L Osiris Therapeutics Inc., Mesoblast Ltd. Canada,
New Zealand
Health Canada, MedSafe 2012 GvHD Allogeneic human BM-MSC
6 Neuronata-R Corestem Inc. South Korea MFDS (KFDA) 2014 Amyotrophic lateral sclerosis Autologous human BM-MSC
7 Temcell HS JCR Pharmaceuticals Japan PMDA 2015 GvHD Allogeneic human BM-MSC
8 Stempeucel Stempeutics Research PVT India CDSCO 2016 Critical limb ischemia Allogeneic human BM-MSC
9 Alofisel TiGenix NV/Takeda Europe, Japan EMA 2018 Complex perianal fistulas in Crohn’s disease Allogeneic human AT-MSC
10 Stemirac Nipro Corp Japan PMDA 2018 Spinal cord injury Autologous human BM-MSC
Reference:
1. Pereira Chilima et al., 2018; Levy et al., 2020
2. Hu H, Zou C. Mesenchymal stem cells in renal ischemia-reperfusion injury: biological and therapeutic perspectives. Curr Stem Cell Res Ther.2017;12:183-7
3. Oliveira-Sales EB, Boim MA. Mesenchymal stem cells and chronic renal artery stenosis. Am J Physiol Renal Physiol. 2016;310:F6-9
No. Product name
1 Queencell
2 Cellgram-AMI
3 Cartistem
4 Cupistem
5 Prochymal, remestemcel-L
6 Neuronata-R
7 Temcell HS
8 Stempeucel
9 Alofisel
10 Stemirac
Company Approved country Regulator Year Indications Product Type
Anterogen Co. Ltd. South Korea MFDS (KFDA) 2010 Subcutaneous tissue defects Autologous human AT-MSC
Pharmicell Co. Ltd. South Korea MFDS (KFDA) 2011 Acute myocardial infarction Autologous human BM-MSC
Medipost Co. Ltd. South Korea MFDS (KFDA) 2012 Knee articular cartilage defects Allogeneic human UC-MSC
Anterogen Co. Ltd. South Korea MFDS (KFDA) 2012 Crohn’s fistula Autologous human BM-MSC
Osiris Therapeutics Inc., Mesoblast Ltd. Canada,
New Zealand
Health Canada, MedSafe 2012 GvHD Allogeneic human BM-MSC
Corestem Inc. South Korea MFDS (KFDA) 2014 Amyotrophic lateral sclerosis Autologous human BM-MSC
JCR Pharmaceuticals Japan PMDA 2015 GvHD Allogeneic human BM-MSC
Stempeutics Research PVT India CDSCO 2016 Critical limb ischemia Allogeneic human BM-MSC
TiGenix NV/Takeda Europe, Japan EMA 2018 Complex perianal fistulas in Crohn’s disease Allogeneic human AT-MSC
Nipro Corp Japan PMDA 2018 Spinal cord injury Autologous human BM-MSC
Reference:
1. Pereira Chilima et al., 2018; Levy et al., 2020
2. Hu H, Zou C. Mesenchymal stem cells in renal ischemia-reperfusion injury: biological and therapeutic perspectives. Curr Stem Cell Res Ther.2017;12:183-7
3. Oliveira-Sales EB, Boim MA. Mesenchymal stem cells and chronic renal artery stenosis. Am J Physiol Renal Physiol. 2016;310:F6-9
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