The Road to Low Cost Universal Cells and Tissues, For Transplantation into Any Patient

An area of intense interest in the academic and biotechnology communities is the development of cells that do not provoke an immune response due to mismatch of cell surface receptors. As a general rule, cells from one individual are rejected by any other individual. It is possible to minimize this outcome by eliminating MHC receptors, but there are other complex interactions between cell surface chemistry and portions of the immune system that can still act as a barrier to transplantation. A number of groups have developed approaches to address specific parts of this problem space, but no one winner has yet emerged. At the end of this road can be found universal induced pluripotent stem cells, enabling the generation of cells of any type, as needed. Those cells can then be used to grow tissues and organs, or in more traditional cell therapies, that are compatible with any patient, greatly reducing cost and logistical challenges.

The prospects of generating specialized cells in a dish that can be transplanted into patients to treat various diseases are encouraging. However, the immune system would immediately recognize cells that were recovered from another individual and would reject the cells. Hence, some scientists believe that custom cell therapeutics need to be generated from scratch using a blood sample from every individual patient as starting material. Researchers here followed a different approach, using gene editing to create 'universal stem cells' (named HIP cells) that are not recognized by the immune system and can be used to make "universal cell therapeutics."

The team tested the ability of these cells to treat three major diseases affecting different organ systems: peripheral artery disease; chronic obstructive pulmonary disease from alpha1-antitrypsin deficiency; and heart failure, increasingly a global epidemic with more than 5.7 million patients in the United States alone and some 870,000 new cases annually. The scientists transplanted specialized, immune-engineered HIP cells into mice with each of these conditions and were able to show that the cell therapeutics could alleviate peripheral artery disease in hindlimbs, prevent the development of lung disease in mice with alpha1-antitrypsin deficiency, and alleviate heart failure in mice after myocardial infarction.

One of the great benefits of this approach is that the strategy of immune engineering comes with a reasonable price tag. It would make the manufacturing of universal, high-quality cell therapeutics more cost effective, could allow future treatment of larger patient populations, and facilitate access for patients from underserved communities. "In order for a therapeutic to have a broad impact, it needs to be affordable. That's why we focus so much on immune-engineering and the development of universal cells. Once the costs come down, the access for all patients in need increases."

Link: https://www.ucsf.edu/news/2021/07/420961/engineered-cells-successfully-treat-cardiovascular-and-pulmonary-disease

Comments

I guess it would be much simpler and cheaper to produce cellular vesicles , which seem to have much more favorable immunological profile. However, in the worst case scenario we might be stuck with the need to culture person-specific cells. It will be always more expensive than off-the shell generic cultures, but still can be doable with correct organization. I can envision automated kits.

What i personally believe/suspect that there will be from 5 to 50 antigen types (akin the blood types) that could be cultured and stockpiled for emergencies and those might be good enough.

Posted by: Cuberat at July 20th, 2021 9:25 AM

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