Page 78 - Mesenchymal Stem cells, Exosomes and vitamins in the fight aginst COVID

Intravascular Mesenchymal Stem Cells to Treat Organ Failure and Possible Application in COVID-19

that use of anticoagulation with low-molecular- been reprogrammed back into an embryonic-like
weight heparin or unfractionated heparin improved pluripotent state that enables the development of
outcomes in severe cases with coagulopathy. any type of human cell. Clinical applications of iPSCs
face several major hurdles, such as low cellular repro-
Stem Cell Therapy in Organ Failure: gramming efficiency, epigenetic memory, oncogenic
Mechanism of Action risks, low efficiency of cardiomyogenesis, and cell
There are many types of stem cells and can be line-to-line variations.
broadly classified as totipotent, pluripotent, and MSCs are found in all the tissues in which they
multipotent cells. Totipotent stem cells cannot only replace diseased or aged cells. MSCs can be obtained
differentiate into all the 3 primary germ layers but from multiple sources and are most easily accessible
also the extraembryonic tissue, such as the placenta. from bone marrow, fat, dental pulp, umbilical cord,
The fertilized egg is the only example. Pluripotent amniotic tissue, synovium, and placenta. However, to
stem cells develop into all 3 germ layers. Embryonic treat organ failure large doses of MSCs are required
stem cells and induced pluripotent stem cells (iPSCs) for clinical efficacy and the most common route of
are classified as pluripotent. Although multipotent administration is intravenous (IV) followed by intra-
stem cells can differentiate into all 3 germ layers, arterial (IA). Hence culture expansion to significantly
they usually develop into 1 or 2 cell lines only. In each increase the number of MSCs remains a prerequisite.
cell line they can transform into different types of Autologous MSCs (adipose and bone marrow) or allo-
cells. The adult MSCs that are most commonly used geneic MSCs (umbilical cord, placental, endometrial,
in regenerative medicine belong to the multipotent and amniotic tissue) can be used for culture expan-
stem cell category. MSCs likely originate from the sion. For autologous purposes, adipose MSCs seem to
mesoderm and have the capacity to differentiate be more desirable than bone marrow MSCs primarily
into a variety of mesenchymal tissue lineages, such as because of the significantly higher number of MSCs
osteoblasts, chondrocytes, and adipocytes . A divid- found in the adipose tissue when compared with the
ing MSC produces 2 daughter cells. One is another bone marrow. Because the use of autologous MSCs
stem cell, quiescent until it is needed, whereas the usually requires an invasive procedure, allogeneic
other divides further and specializes into one or a sources seem attractive. Moreover, in patients with
few types of cells. Such “self-renewal” is essential to organ failure, the harvest procedure has inherent risks
growth and healing. in lieu of suboptimal health. Additionally, the MSCs
The International Society of Cell and Gene from older patients have aging stem cells, which are
Therapy requires a cell to meet all the 3 criteria to be inferior to younger stem cells, such as umbilical cord
defined as an MSC (25): MSCs in terms of proliferative, secretory, and differ-
entiation capabilities. This renders older autologous
1. The cell must be plastic-adherent when main- MSCs less potent compared with fetal stem cells, such
tained in standard culture conditions. as umbilical MSCs. Additionally, allogeneic cells are
2. The cell must express CD105, CD73, and CD90, and not functionally impaired by the patient’s comorbid
lack expression of CD45, CD34, CD14 or CD11b, conditions.
CD79α or CD19, and HLA-DR surface molecules. Additionally, allogeneic MSCs are immunoprivi-
3. The cell must differentiate to osteoblasts, adipo- leged and rarely evoke immune responses in the host
cytes, and chondroblasts in vitro. they express low level surface markers of major his-
tocompatibility (MHC) I and hardly express the sur-
MSCs can also be classified as embryonic, fetal, face markers MHC II. Also, MSCs do not express the
adult, and iPSCs. Embryonic stem cells are derived costimulatory molecules, such as CD40, CD80, or CD8.
from the inner cell mass of the blastocyst. They are Despite the low expression of MHC I, MSCs cannot
immortal and highly proliferative. Ethical issues and activate secondary signals of the immune response,
their propensity to cause tumors precludes clinical which will result in the absent response status of T
utility. Fetal stem cells are mostly obtained from the cells because of the lack of costimulatory factors .
umbilical cord and placenta. Adult stem cells are MSCs also have inherent immunosuppressive activ-
usually sourced from the bone marrow and adipose. ity that can prevent an immune response from the
IPSCs are derived from skin or blood cells that have host. Patients usually do not develop persistent do-

www.painphysicianjournal.com S395