MESENCHYMAL STEM CELLS AND REGERNERATIVE MEDICINE
9 August 2021
15 million blood cells expire and gets regenerated in our human body. There is a group of innate cells that are produced from the bone marrow which is responsible for this regeneration. These are known as the hemopoietic stem cells, if these cells are expired, our lives will also expire.
it’s been said that, mesogenic process is involved in this mechanism, such that the mesenchymal stem cells (MSCs) present in the bone marrow, when stimulated, are able to produce mesenchymal tissues with multipotent stromal cells which in turn are able to differentiate into a number of tissues such as bone, fat, cartilage, and muscle. Numerous studies have illustrated the role of MSCs for tissue regeneration in several animal models or in vitro. Several clinical reports verify the potential efficacy of MSC-based cell therapy; although its effectiveness remains limited, but the outcomes were inspiring.
Current dogma states that all MSCs are derived from pericytes or perivascular cells. These can be contractile elements. for example; in case of Blood pressure, these are the cells that relaxes the cardiac arteries accordingly creating a low or high blood pressure. MSCs are found as perivascular cells and even in large vessels, in the adventitia however not in general connective tissue.
Molecular markers present in these perivascular cells depends on the type of tissue or organ such as in case of Liver MSCs: CD29, CD44, CD73, CD90, HLA-Class I, etc. are the mesenchymal markers expressed. Similarly
Marrow MSCs: Markers of hematopoietic and endothelial cells, are CD11b, CD14, CD19, CD31, CD34, CD45, CD79β, CD117, CD133, CD144, and HLA-DR
Kidney MSCs:CD11b, CD14, CD34, CD45, CD79a and HLA-DR, in addition to surface expression of CD73, CD90, and CD105
Heart MSCs: CD13, CD49b, and CD90
The most commonly used inducing factor for osteogenesis is the bone morphogenetic protein-2 (BMP-2), which is usually immobilized on scaffolds to promote osteoblast differentiation. BMP-2 exhibits a strong osteogenic ability, which can be tested by the osteoblast activity and/or expression of bone markers, such as alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN)
It’s been found that adipose tissue pericytes and MSCs are highly similar and therefore it’s been understood that by using transcriptomic analysis, Pericytes can give rise to MSCs.
Mechanism of MSC synthesis
If an injury occurs there is a Broken blood vessel, such that pericytes comes out of this blood vessels and it differentiates into MScs. Form this MSCs it synthesises locally molecules that stop the overaggressive immune system from interrogating the injured tissue behind it. This is the first line depends of MSCs against overall immune system form setting up. Midwhile these MSCs synthetises a different group of molecules which would regenerate a microenvironment, inhibiting the scarring. therefore, to be precise from one side there occurs immune modulation and on other side performs the anti-apoptotic, anti-scarring, angiogenic, mitotic, and an overall regenerative micro environment.
Example people especially actors who have wrinkles, generally undergo liposuction to rejuvenate and lift the face and neck by injecting liposuction, where a fat is injected to the bulk of skin
MSCs can be a medicinal signalling cell (the injury-specific Drug store) such that it goes into cardiac myocytes and repairs them. In case of MI, when perivascular cells are damaged, MSCs would turn into pericytes, by which they restabilise the fragile capillaries into new during myocardial infarction. Therefore, they provide drugs that would allow our own intrinsic stem cells in those tissues to regenerate the damaged tissue, such that every single tissue in our body has the intrinsic stem cells like cardiac stem cells, liver stem cells, kidney stem cells therefore they have their own innate capacity to regenerate and restore the damaged tissues.
MSC based therapy:
MSCs dock at sites of injury or inflamed blood vessels such that they have an immune modulatory component and a regenerative component which acts as the natural management of innate regenerative potential. Till now clinical trials have been conducted for using MSCs as a regenerative therapy for the following conditions:
Chron’s disease, AMI, chronic heart failure. Kidney failure, rheumatoid arthritis, lupous, primary biliary cirrhosis, Sjogren’s syndrome, type 1 diabetes, auto immune hepatitis.
MSC makes antimicrobial proteins -the human catheliciden antimicrobial peptide. hCAP-18/LL37(such that MSC bound to bacteria and makes LL37) is secreted by hMSCs. In vivo hMSCs effect sepsis induced by bacterial infections. LL37 which is found in breast milk is able to fight against infections, so they are called as defensins
MSCs cell therapy actually worked everywhere in the body. MSCs from different sites and different tissues are sensory such that it senses the microenvironment and act as a hard-wired response profile, for instance if there is MI or stroke and if MSCs are given they goes towards the sensory sites thus producing the appropriate response. Therefore, MSC eighter puts into anti-inflammatory immunomodulatory activity or inflammatory activity. It’s the capacity to sense the microenvironment and to have a complete response profile accordingly.
Drawback of MSC:
MSCs number declines with ageing such that the number of HMSC or Human mesenchymal cells obtained by marrow aspiration declines with age which means that, age-related decline in overall BM MSC “fitness” might lead to problems when using autologous aged MSC for cell- based therapies. Estimates obtained by CFU-F assay says that a new born consists of 1 mesenchymal cell per 10000 marrow cells while an 80-year-old adult would have only 1 MSC per 2000000 marrow cells. Therefore, it’s been proved that MSC declines with ageing. Similarly the doubling time of MSCs in foetus is 1 billion in 30 days however in aged people its 200 cells in 30 Days such that, in babies ,cells divide in every 24 hrs while as compared to a 35 year old person ,it divides only in every 48 hrs and further in a 65 yr. old it divides every 60hrs,which means that as we gets older it takes longer time for cells to divide such that if we culture the cells of a foetus ,at the end of 1 month there can be 1 billion cells while a 35 yr. old will have only 32000 cells and 65m yr. old ill have just 200 cells.
Here comes the role of regenerative medicine, such that it tries to bring up with higher number of mesenchymal cells into the human body irrespective of age by incorporating young healthy cells to stimulate other older cells to behave like a younger and healthy cells
Isolation and production of MSC:
Umbilical cord MSCs id taken and the tissue is dissected and digested with enzymes such that primary culture id obtained which are then transferred to plates under appropriate growth medium and are frozen down in liquid nitrogen so as to make it inactive.
Mesenchymal stem cell in menstrual blood found to be dividing. Menstrual MSCs are found tom be similar to the fat MSCs or marrow MSCs.
Mesenchymal stem cells (MSC) are promising candidates in the emerging field of regenerative medicine. Mesenchymal stem cells control inflammation, modulate the immune system, stimulate regeneration. Most chronic diseases are due to a lack of or dysfunction of mesenchymal and other stem cells. As we age, the number and function of our stem cells declines. Cellular products, molecules, exosomes and micro vesicles are released and stimulate the regeneration of your own stem cells to newer tissue forms. Embryonic stem cells are the stem cells that have the most differentiating potential, but they require optimised environment for these cells to grow. However, the action of stem cells synthesised in different labs are not yet confirmed whether they perform the same action. In a study, conducted to evolve stem cells, a middle-aged woman underwent face lift via stem cells under her eye, had a massive adverse event, because of her stem cells got converted from fat to bone orientation, which made her unable to blink eyes resulting to a removal of the stem cells. Similar kind of a case was noted in patient who did a surgery for macular degeneration, where they did a stem cell injection into the eye, unfortunately they became blind later on.so its always mandatory to have a proper clinical trial and a valid scientific evidence before physicians start using them.
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