Basically all I remember from this lecture is the idea that "mesenchymal stem cells have shown promise in curing basically anything," but I'm going to do my best to show a bit more nuance than that in this blog post.
So what exactly are human mesenchymal stromal cells (a.k.a. human mesenchymal stem cells, or MSCs)? They are adult stem cells that can be obtained from a lot of tissues. MSCs are multipotent and can differentiate into a variety of different tissue types, including bone, fat, and cartilage. As such, they can aid in tissue repair. MSCs also have immunosuppressive and immunoregulatory effects. One of the advantages of using MSCs is that they are hypo-immunogenic, due to low levels of MHC-I and no MHC-II (see here for an explanation on MHC/HLA molecules). They are not recognised by T-cells or NK cells, and thus do not need to be matched before being given to a patient. A patient will usually receive around 2 million MSCs per kilogram of body weight.
As I just said, MSCs can be harvested from many different tissue types. This lecture focused on MSCs harvested from bone marrow. MSCs in bone marrow are derived from stromal stem cells, which are one of two main types of stem cells in bone marrow (the other main type is haematopoietic stem cells, which become blood). MSCs are actually quite rare in the bone marrow, but they can be readily isolated and expanded. To manufacture MSCs, only around 10mL of donor bone marrow is needed. MSCs are sticky, so they stick to the bottom of the flask (which I assume helps in isolating them). To ensure that the cells harvested are actually MSCs, flow cytometry can be used. MSCs will be positive for CD105, CD73, and CD90, but negative for CD34, Cd11b, CD19, CD45 and HLA-DR.
In the bone marrow, MSCs are used in connective tissue scaffolding, supporting haematopoiesis, differentiation, and immune regulation. MSCs can home to inflamed tissue and control inflammatory reactions. It is thought that they do this by secreting soluble factors through exosomes or microvesicles, or by communicating via cell-cell contact. MSCs can have a pro- or anti-inflammatory phenotype, depending on the prevalence of immune mediators in the surrounding tissue. If pro-inflammatory cytokines, such as IFNγ and TFNα are low, then MSCs will display the pro-inflammatory phenotype; if levels of these cytokines are high, then MSCs will display the anti-inflammatory phenotype.
One condition that might be treatable with MSCs is Graft vs. Host Disease (GvHD), which I have discussed here. GvHD occurs when a tissue containing immune cells (e.g. bone marrow) is transplanted into an immunocompromised host. For example, HPC-A (a blood transplant), HPC-M (bone marrow transplant) or cord blood may be given following high doses of myeloablative therapy (high-dose chemotherapy that kills cells in the bone marrow). The immune cells in the transplanted tissue recognise the host cells as "foreign."
GvHD can be either acute or chronic. In the early phase of acute GvHD, there is damage to the tissues, leading to a cytokine storm (a large release of pro-inflammatory cytokines). In the second phase, the donor cells activate and expand. Finally, in the third phase, activated T-cells release pro-inflammatory cytokines, monocytes and NK cells are recruited, and cytotoxic T-cells damage the tissue. Many areas of the body can be affected, and the skin may undergo blistering, scarring, and pigmentation changes. Chronic GvHD usually only affects the skin, but lungs may be affected as well.
MSCs may also be able to treat Host vs. Graft Disease, which is basically a transplant rejection. (Rejection isn't the only thing that could damage a transplanted organ, though. When an organ is suddenly perfused with warm blood, Ischaemia-Reperfusion Injury may result.) MSCs have been trialled in Bronchiolitis Obliterans Syndrome, which is a kind of chronic rejection in which transplanted lungs become fibrotic and less functional. MSCs have been found to localise to the lungs immediately after infusion, before moving to the spleen and liver. MSCs have also been trialled in the treatment of acute renal rejection.
MSCs have also been trialled in some autoimmune diseases (which I suppose you can think of as "Host vs. Host Diseases"), such as Crohn's Disease (see here for more information about Crohn's).
I also have some note in my notebook that MSCs may also be used as a scaffold for growing bone. I guess that gives you something else to do with them once you're done curing the world of all of its ailments. I'm not sure about the details, though, because I didn't expand on my notes, the lecture slides aren't up on LMS yet, and the lecture recording ended there (the lecture went overtime).
Whew! I finally did it! I finally wrote about this week's PATH3304 lectures!
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