MSC have a degree of immuno-suppresive activity and thus are not usually subject to the same immune response as other foreign cells. I recommend the attached review for further information on this subject.

Hello Ajay,

Agreed with Merlin. In case of stem cells as they are naive cells so are not having very specialised kind of differentiated MHC profile on their cell membrane and hance the immunogenic response created in a different host is minimum. eg. I am working on dental stem cells and care which are least immunogenic due to very low expression profile of HLA-DR so it is safe to transplant them in an animal for further studies. 

Thats why they can be used for in vivo studies in animal species without immune rejection..

Hope it helps !

Thanks to merlin

and also thanks to Ajay..

really it is helpful information.

Hi Thanusha,

I second both the former suggestions. I would like to add few more specific details. MSCs are loaded with a lot of cytokines and factors which are immunosuppressive- prostaglandin E2 (PGE2), interleukin 10 (IL-10), IL-6, transforming growth factor-β (TGF-β), indoleamine 2,3-dioxygenase (IDO), and nitric oxide (NO). All these factors help in inhibiting the proliferation and function of major immune cell populations like T and B cells. Also MSCs express very low levels of major histocompatibility complex (MHC) class- I and II molecules on their surface. That effectively further cloaks them from immune soldiers. I believe these characteristics are developmentally important, as the MSCs in the body sometimes have been known to travel to different organs for damage control and repair. I believe that's it in a  nutshell. Best of luck to you in your study. Have a good day.

i agree with researchers , also, The underlying mechanisms are believed to be a combined effect of many immunosuppressive mediators. A majority of the mediators are inducible by inflammatory stimuli, such as nitric oxide (NO), indoleamine dioxygenase (IDO), prostaglandin E2 (PGE2), tumor necrosis factor-inducible gene 6 protein (TSG6), CCL-2, and programmed death ligand 1 (PD-L1) . These factors are minimally expressed in unactivated MSCs unless they are stimulated by several inflammatory cytokines, such as IFNγ, TNFα, and IL. The neutralization of either immunosuppressive effectors or inflammatory cytokines could reverse MSC-mediated immunosuppression. The concept of inflammation-licensed immunosuppression favors a more rational design for the clinical use of MSCs. First, an optimal administration time point should be carefully selected according to the levels and ratios of different cytokines in the body during disease progression. Previous reports have demonstrated that MSC administration after disease onset may be better than at the same time of disease induction in a mouse GvHD model. Second, cytokine priming should be attempted to improve the therapeutic effect of MSCs. Cheng et al reported that IFNγ-pretreated MSCs protected 100% of mice from GvHD-induced death. Third, the therapeutic efficacy of MSCs most likely depends on the nature of different diseases due to the distinct inflammatory environments. Even for a specific disease, the diversity of microenvironments in different tissues may also produce different curative effects of MSCs. Therefore, the precise in vivo mechanism of MSCs may be more complex than observed in vitro. Further defining such mechanisms will help to develop better strategies for the clinical use of MSCs.

Good Luck

Thanks to Glen and Saleh..

I have one doubt in this stem cells only,

when we inject stem cells from one donor to other person, these MSC will differentiate in to like keratinocytes, chondrocytes etc,,

in that case the dna of stem cells of receipeint and donor or totally different,

How these stem cells will grow in that way and live in that different dna environment?

As others mentioned, MSC theoretically have the immuno modulatory function!

T cells, B cells and MQ.

However, I doubt if this is always true!

Hello again Thanusha,

Your doubt is the driving force for many present investigations trying to push MSCs to widespread clinical studies. A lot of dispute is taking place as to what the MSCs do after being transplanted. The only certified observations are that their beneficial effects are very limited after a certain period of time post transplantation. Here's the long story based on various schools of thought:

1. The MSCs because of the microenvironment lower the expression of immunosuppressive factors, hence are eventually rejected.

2. Differentiation: First of all there is no general consensus that MSCs do differentiate into true cells of all lineages (other than osteoblasts, chondrocytes, myocytes and adipocytes) or if they do, they might not form functional cells. So considering they do differentiate, till MSCs retain the capacity for self-renewal and multipotency, the helpful factors are expressed. Once they differentiate though, the factors' expression is stopped and high expression of MHC takes place. This effectively acts as an identification marker for the host immune system to attack the former non-discoverable cells

3. MSCs do not help in tissue repair directly. Rather they release paracrine factors and these go onto stimulate the endogenous cell populations to initiate repair. So here they just act as a reserve for paracrine factors. The MSCs are bound to diminish one day and with them the positive effect of paracrine factors.

4. Transplantation site: Some sites allow immunoprivilege of MSCs like kidney capsule, eye etc., while other sites can be highly immunogeneic. This leads to a belief that only a few organs in the body might be receptive to MSC therapy.

I believe there are more point of views, which I look to our fellow researchers to help us shine a light upon.  Finally to put in a nutshell, if not considering the 3rd point, they eventually are discovered by the host system and thence rejected. But kindly do remember they have been found to be safe in multiple clinical studies (Except in one, where they caused a tumour), just that the benefits declined over time.

Hope this helps you in your present endeavour. Wishing you a good day

Thanks a ton to Glen lester...it really helpful me..thanks again...

These cells show low expression of human leukocyte antigen (HLA ) class I, do not express HLA class II and costimulatory molecules ( CD40 , CD80 and CD86 )

Based on the attached paper I would suggest that 'MSCs are immunoprivileged' is one of the many MSC myths, some others highlighted by Glen in a more complete response. If your injected cells do differentiate (they probably won't) then I think you could assume that any special immune privilege will be lost to give it the same privileges that whatever cell you may claim it has turned into normally has. e.g. if you say it has become a keratinocyte, it will be as immunoprivileged as a normal keratinocyte (i.e. not at all)

a part of your question that I don't think has been answered is specifically following human MSC injection into rats. Some researchers have started using immunosuppressor with this kind of experiment. Very common when administered systemically is that the rodents are lethally irradiated, destroying their immune system. where there is no irradiation and no immunosuppression, you will find that most studies report transient 'grafting'.

Article Allo-Reactivity of Mesenchymal Stem Cells in Rhesus Macaques...

Partly is certainly due to the immune modulatory ability of MSCs however, we should consider the possibility of a delay response that may end up to some modmodifications inside the recipient DNA. Any change or alteration in animals with fast metabolic rate like mice for instance will be probably pass unnoticed due to their short life span.....it would be of critical importance to see what would happen in mammals such as primates or elephants where there would be enough time to evaluate any structural modification....

You must read the literature carefully.  There are many published reports documenting an allograft response in xeno-recipients from most species including babbons, rhesus macaques, swine, and rodents.  The notion that MSCs are immune-priviledged has largely evolved from human clinical trials, which fail to see acute allograft responses following transplantation of MHC mismatched cells.  However, there are reports of patients experiencing such symptoms but they are not widely publicized.  There is also evidence that allogeneic MSCs do not provide as potent a benefit compared to autologous cells in some trials that have been published but you must evaluate the data carefully.  In many cases the authors of these papers are aiming to demonstrate that allogeneic cells are as effective, so the title and abstract are often biased to this effect.   The big problem is that there are few comparative studies on the topic in humans.  

Thanks to All...

They do not have MHC class2 and express the MHC class1 in the minimum level.

They do not have MHC class2 and express the MHC class1 in the minimum level.

But Do we know if MSCs of animal origin express any of the Glycan antigens such as Neu5GC. I understand from literature (Dr Ajit Varki's lab) that humans do not produce such antigens. So what happens when animal stem cells get injected into humans ? Do they induce an immune response, make immune complexes with existing low level antibodies in humans(apparently produced by consumption of animal prioducts, like beef), cause secondary immune response (as immune complexes do) and GVH. Hope Hamed can answer these questions as it is not just lack of MHC 1 and 2 antigens.

I think Dr Phinney is very correct,

In addition i would like to add two points

1 Humans do not produce Certain Glycan antigens , Such as Neu5GC, and animals do. If the animal cells are transfused into humans we can expect reactions to xeno antigens, even if MHC class 1 and 2 are zero to minimal.

2 On the contrary, human cells in animals are likely to generate responses to MHC antigens and if they are weekly expressed the chances are lower to see any reactivity (alt least acute).

MSCs lack MHC class 2 and do not trigger the rigorous immune response as any other foreign cells because they show immunosuppressive activity