TSB2018 - focus on regenerative medicine
Note from Annual Meeting of the Thai Society for Biotechnology and International Conference (TSB 2018)
I enjoy the tissue engineering part at the most.
Tissue engineering preparation
1. facing the issue production inconsistency - vary lot by lot
2. try to use robot arm to solve the issue, however, there are some steps which the robot arm could not replace the human labor. The robot arm in some extent is much slower and less delicate in term of movement than human labor.
3. learning that Thailand so far could not produce the robot arm + clean room platform - KMUTT (Bio-processing unit - pilot plant) makes the collaboration with Japan -> to make this comes to reality -- though Thai side could not produce the robot arm, at least, the team can make the software to control the arm as well as to design the workflow.
4. There are many things that all the physicians mentioned, especially when applying to the patients;
- iPS technology was awarded by the Nobel prize in the year of 2012 (Prof. Shinya Yamanaka - the founder)
- the major problem of tissue transplantation is that it is degraded over time.
- there is the urgent need for the basic research to prevent such a thing (degrade over time and trying to prolong the tissue grafts as long as possible so the patient don't have to undergo surgery quite year in and year out)
- environmental factors (stromal cells as well as microenvironments) are important to extend the tissue graft.
- once the tissue from patients have been isolated and propagated in the larger amount - there is the need to determine the quality of iPS cells - currently, the team uses telomere length (to measure the shelf-life of stem cell, it has been known that the cell is heterogeneity even though they are all stem cell) and other types of markers which indicate its origin and function.
- circadian genes are part of the quality of stem-cell and it requires more investigation on the relationship between the stemness and the circadian gene profiles.
- immunological function - even though, the engraft tissue is originally from the same patient, however, the immune can detect those as the foreign materials - therefore, research is needed to answer this question, one possibility has been raised is the HLA, it might require genome editing to make it more compatible.
- to prolong the tissue engraft -- it has to be prepared as the combo cells (functional cells + supporter cells -- engraft as a matrix)
- mimetic -- avoid the detection as foreign material by the immune system -- the speaker gives the examples of cancer cells which can avoid the immune detection (the speaker gave the example between bone metastasis vs osteoblast which the molecular profiles are pretty similar but bone metastasis can avoid the host immune system).
- from the surgeons' point of view, they need the tissue which is easy to engraft during operation, not requiring post-manipulation during the surgery (my guess it would reduce the complications that might occur during/after the operation).
- the organ that they first start --> cornea -- it is the isolated organ and can be regulated if there is the complications occur.
- they start with the patients who have "Limbal Stem Cell Deficiency" (must have one eye left to isolate the stem-cell) --> they have found out that even though the defect cornea has been replaced with the new one, the disease still comes back - then they start to realize that not only corneal epithelial cells (pad) have to be engrafted but also the stem-cell must be required to prolong the layers. Another cause is the rejection due to the host immune system --> it has been observed that the rejection has been related to the HLA. Therefore, genome editing on HLA (biomimicry) might help to reduce the rejection rate (so far they use immuno-suppressant to reduce the rejection but the patients have to take this drugs in long-term to prevent the rejection which cost a lot of money and there is the side-effect by using this drug).
- for the brain --> very challenging --> requires 1.right cell type, 2.right location, and 3.right connection
5. perspective from bioengineering;
- using robot to reduce the cost in term of infrastructure and human error from routine (fatigue)
- logistic from the bio-pilot plant to hospital (how?)
- so far, there are the high demand but the supply is very limited, it could not be done in the other country since it requires patients' specific tissue to be isolated and cultured.
- the bottleneck is the clinical trial level --> can be produced --> never tried in the reality
- passage number does affect the cellular quality and it varies according to each cell type.
- they really wish to see the "biobank" where allogenic could be done --> this requires biobanking facility to do typing match between donor and receiver (need joint venture agreement among physician, scientist, law maker, people).
- the information of disease prevalence is needed for the Thai people, either regenerative disease or others -- the speaker mentioned that Thailand lacks this information.
- Basic research in Thailand is actually urgent needed rather than the clinical practice since the later one goes much far beyond than the basic research.
6.CAR-T cells --> still autologous --> required genome editing on HLA to reduce the rejection
7. No basic research will cause the country less competent for competitiveness on the innovation otherwise we can only copy from the country but cannot generate our own technology.
8.GMP standard -- two current standards 1.FACT and 2.AABB
9.GTP -- Good tissue practice
10. In the very near future, advanced therapy products will become more prominent, however, it is very expensive, there is the urgent need to reduce the cost which everyone who needs can access.
11. Stem-cell quality
- though the morphology looks pretty much the same, however, things inside is different in each cell which causes inconsistency in term of production (require single cell sort based on best criteria?)
- quality marker --> chromosomal stability, stemness
- stem-cell which is cultured within the media is actually still different from the host (even though it is isolated from the same patient but the property is changed once it is cultured in vitro).
- Bottleneck of advanced therapy products; 1. production in large scale in thailand where the resource is limited and contamination is part of the problem due to the tropical area (clean room has different type of classes which require different regulations). 2.regulation from FDA 3.logistic to transfer those materials to the other hospitals in Thailand
----------------------------
biological | engineer |
----------------------------
--> interface between these two areas must be met to create bioprocess factory
Traditional tissue engineer;
1.sigle cell injection
2.creating the scaffold for cells to attach
Modern -- change to "cell sheet engineering"
Slide credits;
I enjoy the tissue engineering part at the most.
Tissue engineering preparation
1. facing the issue production inconsistency - vary lot by lot
2. try to use robot arm to solve the issue, however, there are some steps which the robot arm could not replace the human labor. The robot arm in some extent is much slower and less delicate in term of movement than human labor.
3. learning that Thailand so far could not produce the robot arm + clean room platform - KMUTT (Bio-processing unit - pilot plant) makes the collaboration with Japan -> to make this comes to reality -- though Thai side could not produce the robot arm, at least, the team can make the software to control the arm as well as to design the workflow.
4. There are many things that all the physicians mentioned, especially when applying to the patients;
- iPS technology was awarded by the Nobel prize in the year of 2012 (Prof. Shinya Yamanaka - the founder)
- the major problem of tissue transplantation is that it is degraded over time.
- there is the urgent need for the basic research to prevent such a thing (degrade over time and trying to prolong the tissue grafts as long as possible so the patient don't have to undergo surgery quite year in and year out)
- environmental factors (stromal cells as well as microenvironments) are important to extend the tissue graft.
- once the tissue from patients have been isolated and propagated in the larger amount - there is the need to determine the quality of iPS cells - currently, the team uses telomere length (to measure the shelf-life of stem cell, it has been known that the cell is heterogeneity even though they are all stem cell) and other types of markers which indicate its origin and function.
- circadian genes are part of the quality of stem-cell and it requires more investigation on the relationship between the stemness and the circadian gene profiles.
- immunological function - even though, the engraft tissue is originally from the same patient, however, the immune can detect those as the foreign materials - therefore, research is needed to answer this question, one possibility has been raised is the HLA, it might require genome editing to make it more compatible.
- to prolong the tissue engraft -- it has to be prepared as the combo cells (functional cells + supporter cells -- engraft as a matrix)
- mimetic -- avoid the detection as foreign material by the immune system -- the speaker gives the examples of cancer cells which can avoid the immune detection (the speaker gave the example between bone metastasis vs osteoblast which the molecular profiles are pretty similar but bone metastasis can avoid the host immune system).
- from the surgeons' point of view, they need the tissue which is easy to engraft during operation, not requiring post-manipulation during the surgery (my guess it would reduce the complications that might occur during/after the operation).
- the organ that they first start --> cornea -- it is the isolated organ and can be regulated if there is the complications occur.
- they start with the patients who have "Limbal Stem Cell Deficiency" (must have one eye left to isolate the stem-cell) --> they have found out that even though the defect cornea has been replaced with the new one, the disease still comes back - then they start to realize that not only corneal epithelial cells (pad) have to be engrafted but also the stem-cell must be required to prolong the layers. Another cause is the rejection due to the host immune system --> it has been observed that the rejection has been related to the HLA. Therefore, genome editing on HLA (biomimicry) might help to reduce the rejection rate (so far they use immuno-suppressant to reduce the rejection but the patients have to take this drugs in long-term to prevent the rejection which cost a lot of money and there is the side-effect by using this drug).
- for the brain --> very challenging --> requires 1.right cell type, 2.right location, and 3.right connection
5. perspective from bioengineering;
- using robot to reduce the cost in term of infrastructure and human error from routine (fatigue)
- logistic from the bio-pilot plant to hospital (how?)
- so far, there are the high demand but the supply is very limited, it could not be done in the other country since it requires patients' specific tissue to be isolated and cultured.
- the bottleneck is the clinical trial level --> can be produced --> never tried in the reality
- passage number does affect the cellular quality and it varies according to each cell type.
- they really wish to see the "biobank" where allogenic could be done --> this requires biobanking facility to do typing match between donor and receiver (need joint venture agreement among physician, scientist, law maker, people).
- the information of disease prevalence is needed for the Thai people, either regenerative disease or others -- the speaker mentioned that Thailand lacks this information.
- Basic research in Thailand is actually urgent needed rather than the clinical practice since the later one goes much far beyond than the basic research.
6.CAR-T cells --> still autologous --> required genome editing on HLA to reduce the rejection
7. No basic research will cause the country less competent for competitiveness on the innovation otherwise we can only copy from the country but cannot generate our own technology.
8.GMP standard -- two current standards 1.FACT and 2.AABB
9.GTP -- Good tissue practice
10. In the very near future, advanced therapy products will become more prominent, however, it is very expensive, there is the urgent need to reduce the cost which everyone who needs can access.
11. Stem-cell quality
- though the morphology looks pretty much the same, however, things inside is different in each cell which causes inconsistency in term of production (require single cell sort based on best criteria?)
- quality marker --> chromosomal stability, stemness
- stem-cell which is cultured within the media is actually still different from the host (even though it is isolated from the same patient but the property is changed once it is cultured in vitro).
- Bottleneck of advanced therapy products; 1. production in large scale in thailand where the resource is limited and contamination is part of the problem due to the tropical area (clean room has different type of classes which require different regulations). 2.regulation from FDA 3.logistic to transfer those materials to the other hospitals in Thailand
----------------------------
biological | engineer |
----------------------------
--> interface between these two areas must be met to create bioprocess factory
Traditional tissue engineer;
1.sigle cell injection
2.creating the scaffold for cells to attach
Modern -- change to "cell sheet engineering"
Slide credits;
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