At the recent RPI stem cell and bioengineering meeting, the Neural Stem Cell Institute’s Sally Temple talked about her group’s intriguing retinal pigmented epithelial cell (RPE) research.
With the broad focus of attention in the world of RPEs mostly on those derived from either human ESC or IPSC, it was exciting to here about the adult RPEs that Temple’s group has isolated and characterized (e.g. see this paper).
Although only about 3% of cells isolated from the human retina turn out to be retinal stem cells, Temple reported that they can be scaled to provide plenty of potential doses (see below).
One of the remarkable things about these stem cells is that they can make beautiful RPEs and also perhaps through some kind of EMT, they can generate cells of the mesenchymal lineage (see image below).
They are hoping to have an IND in the next couple years. I’m very curious how the adult RPEs compare to those made from pluripotent stem cells.
I also asked Sally after the meeting to give a big picture perspective on this work:
“My experience in translating the discovery of RPE stem cells towards a therapeutic for age-related macular degeneration is that it is an intensive team effort. You really need to have experts in different aspects of the science, animal modeling, safety testing, regulatory science and clinical disease, both doctors and patients, all working together. Our experience has been amazing, everyone on the team is working so hard to create this new therapeutic. You also need substantial funding, and we have to thank the NYS NYSTEM program for creating this incredible opportunity via their clinical translation program.”
I’m curious what the pluripotent stem cell-derived RPE fans (e.g. Ocata, the IPSC RPE team in Japan led by Masayo Takahashi, etc.) think of this adult RPE approach.
Dear Paul,
Thank you very much for being so active with this stem cell blog to keep people informed, up to date and providing a platform for discussion. I have been following your blog ca. 1.5 years (sometimes on a daily basis, sometimes very infrequently) and I really like it, but one thing that I have not encountered so far (maybe I missed it) are reports on the advances in adult stem cell science or a side-by-side discussion of putting ESC, iPSC and adult stem cells in a perspective from an expert like you. The trigger for writing this reply is obviously this post on the RPEs and you are raising the right question what do experts in another stem cell field think of those newly isolated stem cells? I am just asking myself what do you think of the studies of Hans Clevers (e.g. liver, pancreas adult stem cells), Richard Schlegel (e.g. skin, cervix adult stem cells) or Howard Green/Elaine Fuchs (adult skin stem cells). Maybe, Hans Clevers is the most suitable to mention in that incomplete list since he is quite active and currently outstanding in terms of output and trying to push his stuff from bench to bedside. Just a humble observation and note from me :).
Thanks and best regards,
Willy
Really exciting work!
I’ve had a feeling for many years that many, if not all tissues, harbor cell populations that are capable of doing what the RPESCs are doing here. From an evolutionary perspective, this would make sense as repair and regeneration for the length of a human lifespan obviously will require “raw material”, so to speak. I personally find the possible existence of VSELs (discussed elsewhere on this Blog) attractive as their existence would enable the continual creation and “topping off” of pools less pluripotent, more defined progenitors, although I’m also well aware of the skepticism and excellent points made by many of my colleagues. Anyway, as mesenchymal stem cells (MSCs) are very often perivascular in distribution, really any tissue in the human body that’s well-vascularized should have resident MSCs or MSC-like/MSC-capable cell populations. It would be interesting to conduct deep genetic analyses of RPESCs to see how they compare with other MSC types. Additional questions such as gender, ethnic, and age-related changes in this cell population would also be really fascinating.
One point, though: I believe that this work would benefit greatly from being redone away from FBS. I’ve always been very skeptical of the effects of fetal bovine serum on cells, in general, and multipotent/pluripotent cells in particular. A serum-free solution would need to be worked out, I think, before any thoughts of therapeutic development should be put forward. I’d also recommend investigating growth and multipotency under hypoxic conditions, which is really (in my opinion) a more realistic promoter of “stemness”. I’d also advise getting away from Matrigel as an ECM substrate as it’s too loosely defined.
Cheers!
I had a go at reading the paper. (It took me many visits to Wikipedia and other sites for background info.) I was very impressed. What a huge effort goes into characterizing these cells!
So what’s the general principle: if one wants to culture-expand cells, look first for cells where division has been turned off at an early stage… I can see why this paper might be a game-changer.
I saw a paper in Nature (can no longer find the ref) where CNS cells were suggested to make a constant effort in order to keep themselves from dividing. (OK, my language is probably bad biology, but I hope you know what I mean.)
Hello, congratulations for the great work! My mom has optic neuritis because she got intoxicated by Ethambutol (she got TB and is a renal patience). is there a chancethat this could help her? Please if you advice me to take her somewhere where fetal stem cell could work for her?, please let me know. Thank you in advance!