First up on the seminar circuit this semester is Mr. Ray Vaio. He will soon be posting an article or two below for background reading purposes. I encourage all faculty and graduate students to attend his seminar on Friday, January 23rd at 1:00 PM in the Ward Beecher Science Hall auditorium.
Articles for friday's seminar
ReplyDeletehttp://www.math.pitt.edu/~cbsg/Materials/Wound_Healing_Overview.pdf
http://www.researchgate.net/publication/6313469_Autologous_bone_marrow-derived_cultured_mesenchymal_stem_cells_delivered_in_a_fibrin_spray_accelerate_healing_in_murine_and_human_cutaneous_wounds/file/e0b49529f225b35417.pdf
For the time being, it appears that links posted in these comments will have to be "copied and pasted" into your web browser to view the articles the reader has provided. I will look into how to overcome this problem.
ReplyDeleteArticles for seminar on Friday, January 30th
ReplyDeletehttp://ac.els-cdn.com/S0002870314001689/1-s2.0-S0002870314001689-main.pdf?_tid=ec3ede1e-a326-11e4-802a-00000aacb361&acdnat=1422035009_55e6667f0658cc5f33d1cece70760c54
http://ac.els-cdn.com/S0735109713013971/1-s2.0-S0735109713013971-main.pdf?_tid=17c5e546-a327-11e4-9aad-00000aab0f6b&acdnat=1422035082_d6f8ddeb62a7ff115a48234578beb390
Ray Vaio’s presentation took us through the typical three phases of wound healing and how this process is currently being enhanced through the introduction of bone marrow-derived mesenchymal stem cells (BMSC). It has been found that due to the multipotent nature of these BMSCs, topical application either within CollaTape or intradermal injection, yielded results of higher tensile strength, increased cell proliferation, and angiogenesis.
ReplyDeleteWhy do you think these cells are allogenic in the canine model and do you believe, with further testing, the same results will be found in the human model?
They were able to use allogeneic cells in the canine model due to an extremely rare characteristic MSCs possess which isn't normally seen in most other cells, and that is they have a way of suppressing the host's immune system to the effect that it does not reject those transplanted MSC. I do feel that similar results would be found in humans, since dogs have a homolog to the human major histocompatibility complex that works in a similar way to differentiate between foreign molecules and self molecules, but that's just a hypothesis and would obviously need to be subjected to the scientific method before i could say for sure.
DeleteThis may seem like an impertinent question; however if MSC's have an internal ability to suppress the host's immune reaction, what has been the main limitation in using MSC's in allogeneic transplantation (which I've understood to mean cells/tissue from a different host) ? Especially if, as you've mentioned we, have a genetic capability to differentiate host/foreign cells. I agree with everyone so far; the prospects for human application are promising, it seems. Humans are so complex and the major disadvantage is the large detrimental affect should experimental trials go wrong.
DeleteI think you did a great job presenting. I was especially a fan of your meticulous explanation of your data graphs/tables. People tend to skip over those details as they seem obvious to the presenter.
Thanks! And as far as i was able to find out, the fact that they don't show rejection was a fairly recent finding and before they would allow a human study I'm sure there needs to be a minimum amount of successful experiments in lower mammals
DeleteThis may be a redundant question. Since the major histocompatibility complex is homologous among mammals, is it possible to used MSCs from a different organism and give it to human for wound healing and if so would yield similar results? The reason I ask is because the way we utilize other organisms (i.e. pigs) tissues.
DeleteRay did a very good job presenting. I feel he presented the information in a manner that allowed for someone with a week understanding of immunology to comprehend the data
Response to Summary
ReplyDeleteRay’s presentation highlighted a fascinating and innovative medical technique that I was not aware of beforehand. The ability of BMSC-based treatments to produce potentially stronger tissues during the healing process is amazing. Obviously these type of procedures have a long way to go before they can be tested on humans, but this type of work yields a lot of promise for individuals who suffer from ineffective healing of wounds such as the elderly or diabetic patients as Ray mentioned in his presentation.
Response to Question
Determining the potential outcomes of such procedures on humans is obviously difficult when there are only animal models for comparison. If/when these procedures were used for humans, there would at least be the potential to add in medications that help prevent possible rejections of genetically dissimilar donor cells.
Response to summary: Ray did a great job on his presentation and presented a next generation concept of essentially improving our body’s ability to heal itself. Canine and murine models are a ways off from people, but the results are impressive. The results also hint at the importance of understanding and properly accounting for the genetic compatibility of same-species tissues/cells between donor/patient and how such issues could potentially be overcome.
ReplyDeleteResponse to question: This question has an extensive number of variables that go along with it. In addition to the potential for medical treatment as Sarah said, would human-based trials have any possibility of being as systematic as the ones performed on the canines? Each and every wound studied on the canines was methodically made. Would the nature/size of human wounds that were tested affect the outcome for better or worse? Would individuals be tested in groups based on wound characteristics when this treatment was still in early development for human use?
I hope i have interpreted the questions rightly and am answering your questions based on my interpretation. Please correct me if i my interpretation is wrong.
ReplyDeleteTo your first question, i think the cells (BMSCs) were allogenic in the canine model because the transplanted cells were sourced from an unrelated species.
To your second question, i think with time the success of wound healing using BMSCs in human would yield positive result but it is going to be complicated and would require caution. I would paint two scenarios;
1. If autologous BMSC were used, the need to worry about histocompatibility barrier and graft versus host disease during transplantation is greatly reduced. How about if the host itself is suffering from severe leukemia, multiple myeloma, lymphomas etc, and every cells in him/her has been plagued with cancer related diseases, do you think autologous BMSC would be a good choice for would healing therapy?
2. Allogeneic BMSC transplant seems to be the obvious answer to the above question. The problems with this therapy would be compatibility with the donor in terms of HLA typing (reiterating Sarah's point). We want to avoid rejection, so matching is of great importance.When a match is found, caution still needs to be taken so that the donors BMSC are not seen as foreign when given to the host. How do we do that......render the host immune system defenseless so that it does not attack the donor cells.Am pretty sure in an immunocompromised individual he/her is at the mercy of various infections and he/she would have to be monitored to avoid nosocomial infection because am sure he/she would have a long hospital stay.
However, worthy of mentioning was Ray's statement during the presentation. He said that there is further research going on with the BMSC so as to eliminate the need to worry about rejection during transplantation (BMSC advantage over disadvantages of skin grafting for wound healing......that would be only if it works). Until the research yields a positive result in terms of eliminating the need to worry about rejection during transplantation, this therapy also has pitfalls like skin grafting (aside the pains associated with skin grafting).
So back to your question, would it work in human with time and further research........everything is possible in science.
MSCs express little HLA. This potential reaction is likely overcome by their ability to suppress the activation of CD4+ and CD8+ T cells while promoting the activation of T regulatory cells (these cells suppress the immune system and prevent over-reaction) through the secretion of specific cytokines.
DeleteIn fact, one study I have read concluded that implantation of MHC-mismatched cells into a primate resulted in no adverse effects and that HLA-mismatched cells are safe to use for cell therapy.
Response to summary: I thought Ray did an excellent job going through the background and methods very smooth as if it was his own project. The three methods that he covered in order worked great and was a steady flow to the talk. The use of BMSC, injections and skin graphs could have some serious benefits for humans.
ReplyDeleteIn response to the question, I believe there is a good possibility that the BMSC's from allogenic humans is possible. From the canine and murine data, the cells proliferated just like new cells in that area and actually sometimes showed increased properties. In one publication (Hare, JM, et. al. 2013), they found there are low incidence rate of predefined treatment-emergent serious adverse events (SAEs) in both allogenic and autologous BMSC's in humans. Even though there was low SAEs in both, the allogenic patients showed no improvement in results compared to baseline, or lower results in caparison to the autologous BMSCs.
Response to Ray's presentation:
ReplyDeleteRay really set the bar high with his presentation. It was interesting to hear how bone-marrow-derived mesenchymal stem cells are being used in wound healing studies. It will be interesting to see how knowledge obtained from the use of animal models within these studies will be applied to human medical interventions.
Response to the question:
I found an article that discussed how researchers transplanted adult bone-marrow-derived mesenchymal stem cells, using a bilateral allogenic transplantation method, into patients that were diagnosed with Parkinson’s Disease in order to see if they could halt disease progression and possibly increase their daily function. 12 patients with varying stages of Parkinson’s was used within this study. They obtained cells from donors that were 18-30 years of age, processed them, and transplanted them into their sub-ventricular zone around their lateral ventricles. After the procedure, patients that were in the early stages of Parkinson’s showed improvement in daily functions and a temporary decrease in progression of the disease. Thus, showing that allogenic BSMC’s can be possibly used within humans. Only further testing with larger population size will confirm this.
Venkataramana, N. K., Pal, R., Rao, S. V., Naik, A. L., Jan, M., Nair, R., & ... Chaitanya, K. (2012). Bilateral Transplantation of Allogenic Adult Human Bone Marrow-Derived Mesenchymal Stem Cells into the Subventricular Zone of Parkinson's Disease: A Pilot Clinical Study. Stem Cells International, 1-12. doi:10.1155/2012/931902
First of all, awesome job Ray. You did really well presenting pertinent and relevant information necessary to understanding the subject.
ReplyDeleteThere have actually been some studies analogous to the one Ray presented using human subjects. MSC treatment have been shown to incredibly promising for several applications. However, there is a lot of specifics and protocols which must be worked out and researched before they are seen as a practical and widely utilized therapeutic including delivery, dosage, and standardization of culture conditions when expanding extracted MSCs.
One particular instance of uncertainty for the use of MSCs for broad clinical use is the variance in their cell surface protein expression. MSCs isolated from allogeneic sources have been shown to exhibit quite a bit of heterogeneity in their expression profile. However, this is not currently thought to be of much issue, as immunogenic reactions with MSCs are rare if at all occurring.
Also, there may be some concern for the use of animal-based serums which are heavily relied upon for cell culture. The exposure of potential xenogeneic proteins may cause some concern, but there is increasing use of platelet lysate solutions and other serum-free media to circumvent this possible interaction. Although obtaining sufficient amounts of these biological alternatives for culture may be difficult.
There has been shown to be more or less no difference in the functional properties when allogeneic cells are utilized rather than syngeneic. This is promising information for potential treatments, since injuries would often necessitate immediate MSC application and the employment of syngeneic MSCs would require time delays required for isolation and in vitro expansion before use. Thus, pre-prepared allogeneic cells could be readily utilized without fear of rejection or adverse immunogenic responses. However, there is little information on whether the immunosuppressive characteristics of MSCs can lead to increased sensitivity to tumor formation and opportunistic pathogens.
Furthermore, there would complications for an individual necessitating MSC treatment such as a patient experiencing chronic non-healing wounds. MSCs extracted from diabetic patients experiencing chronic wounds have been found to somewhat defective and have diminished abilities for cell chemotaxis, angiogenesis, and the secretion of soluble factors involved in wound healing mechanisms. Thus the application of this person’s native MSCs would likely be unsuccessful for wound closure.
Ray you did a great job presenting and explained everything very well!
ReplyDeleteI believe that researchers will be able to use syngeneic MSCs in humans. The research papers I looked at with my paper (links above) shows that researchers are able to extract MSCs from human adipose tissue and bone marrow and differentiate them into cardiopoietic cells for cardiac "wound healing". So I see a strong possibility that researchers will able to derive MSCs from humans to aid in wound healing.
I think Ray did a really great job explaining an area of biology that I personally know very little about. I, like everyone else, believe that there is definitely potential for MSCs to be influential in human wound healing. However, there are definitely risks associated with it. I'm curious if there have been any ethical concerns related to these studies in which allogeneic cells were used?
ReplyDeleteI agree with everyone else that there is strong potential for the use of allogenic BMSC in human wound healing. As a couple people have mentioned, they have already transplanted allogenic BMSC’s into humans with success. Everyone’s main concerns seem to be possible rejection and immunosuppression to avoid rejection. There was an article published in 2005 titled “Mesenchymal stem cells avoid allogenic rejection.” This article can be found here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1215510/pdf/1476-9255-2-8.pdf. The article describes three ways in-vitro human BMSC’s avoided rejection on their own. With this research and all the scientific effort that’s being directed toward studying the possibility of using these cells for wound healing, some clever scientists somewhere will eventually figure out a proper and successful method of BMSC transplantation into human wounds.
ReplyDeleteFolks, I am VERY impressed with your responses and your thoughtfulness in your replies. Let's keep this thing rolling!
ReplyDeleteI will soon be posting the next announcement for Gabriella's seminar this week. Keep up the GREAT job. This is exactly how I had hoped this blog experiment would work!
I am also impressed by your responses.
ReplyDeleteI agree with Josh's comment that this topic seemed next generation. You'll have to forgive my ignorance on this topic, but is this process restricted to tissue type? Gabriella had previously mentioned cardiac wound healing, so I imagine this process can be used for very adaptive purposes. However, I think we're all in agreement that Ray's presentation was very interesting and informative.
ReplyDeleteArticles for seminar Feb 6th
ReplyDeletehttp://www.sciencedirect.com/science/article/pii/S0042682213002596
http://www.jimmunol.org/content/174/5/2453.full.pdf+html