VSELs Could Help the Body Repair Age-Related Damage

vselsIt is widely accepted that stem cells are involved in tissue regeneration. It is also widely accepted that (in most organs) stem cells are vanishingly rare. So: if there doesn’t happen to be a stem cell adjacent to a site of damage, how can stem cells be involved in the process of tissue repair?

One possible answer: There might be more stem cells than we think, because we’ve been missing them for some reason. This possibility (”both”) is strongly supported by the recent findings of Zuba-Surma et al., who have discovered a population of tiny pluripotent cells (termed, appropriately, very small embryonic-like, or VSELs) scattered throughout the body.

Very small embryonic-like stem cells in adult tissues—Potential implications for aging

Recently our group identified in murine bone marrow (BM) and human cord blood (CB), a rare population of very small embryonic-like (VSEL) stem cells. We hypothesize that these cells are deposited during embryonic development in BM as a mobile pool of circulating pluripotent stem cells (PSC) that play a pivotal role in postnatal tissue turnover both of non-hematopoietic and hematopoietic tissues.(cont.)

During in vitro co-cultures with murine myoblastic C2C12 cells, VSELs form spheres that contain primitive stem cells. Cells isolated from these spheres may give rise to cells from all three germ layers when plated in tissue specific media. The number of murine VSELs and their ability to form spheres decreases with the age and is reduced in short-living murine strains. Thus, developmental deposition of VSELs in adult tissues may potentially play an underappreciated role in regulating the rejuvenation of senescent organs. We envision that the regenerative potential of these cells could be harnessed to decelerate aging processes.

Note that both VSEL number and potency diminish with age, consistent with the decrease in proliferative and regenerative capacity that we see in older animals. (And recall that diminishing stem cell potency is just one side of the story: over the course of aging, tissue microenvironments themselves grow more hostile to stem cell growth and function).

The small size of the VSELs, along with their dispersal throughout the body, might explain why they’d been missed up until now. It makes sense that cells devoted to long-term storage of regenerative potential would be very little: other than surviving and maintaining the ability to respond to proliferative signals, they wouldn’t really have much in the way of functional requirements, and wouldn’t need much more than a nucleus, a membrane, and extremely vigilant signal-transduction pathways — the latter ready to awaken the dormant cell when it’s time to turn into a proper stem cell, divide, and differentiate. In a sense, then, these VSELs are not so much progenitors as “progenitor progenitors”, the of regenerative capacity lying silent until they are needed.

(Extending this admitted over-interpretation — small size, after all, does not mean low metabolism, but I’m reasoning by analogy to spores and other very small totipotent cellular forms — another advantage of keeping stem cells metabolically inactive is that they would be less likely to suffer mutations or other damage that could convert them into cancer stem cells.)

Required skepticism: VSELs are both brand new and (so far as I can tell) idiosyncratic to a single group’s work. Before we get too worked up about this, I’d like to see the work reproduced by other labs and in other systems. Hopefully that sort of confirmation is already underway.

Embryonic Stem Cell Research: Your Thoughts

I have been waiting for stem cell research to be permitted again in a way that may actually help us, so am delighted that President Obama has reversed the ban on federal funding. I do not believe that there will be anything that happens in my lifetime that will change things materially for me, but I hope research will help our younger generations.

More Fallout from Notre Dame

The bishops of the United States will meet in San Antonio next month and there is a new agenda item for them: Deal with the fallout from the controversy surrounding Notre Dame’s bestowal of an honorary degree upon the President.President Obama

At the center of that debate has been a document the bishops issued in 2004 entitled “Catholics in Political Life.” As the title indicates, it was unclear to many of us, including Notre Dame’s President, Father John Jenkins, C.S.C., why a document so entitled would even apply to President Obama who is not a Catholic at all. And the text was issued by a committee set up to focus on (and the text only refers to) “Catholic politicians.” Bishop John D’Arcy replied that if there was any question, Father Jenkins should have asked him. To clarify for everyone, however, the bishops need to decide if the document and the strictures it contemplates are meant to apply to everyone or just to Catholics.

Most opponents of Notre Dame’s decision to honor the President focused on one part of the text: “The Catholic community and Catholic institutions should not honor those who act in defiance of our fundamental moral principles.” Now, it is a fair question whether Barack Obama, in promising policies that seek to reduce the abortion rate, is acting in defiance of anyone’s fundamental moral principles. (The abortion reduction language he used throughout the campaign and again at Notre Dame certainly annoys and angers some pro-choice activists.) There was a time when Catholics could be skeptical of the claim by some that they were “pro-choice but not pro-abortion” but Obama seems to making that a distinction with a difference.

It is also the case that virtually every American politician acts in defiance of some fundamental principle of the Catholic Church. Former Vice-President Dick Cheney is justifying the use of torture (and his arguments are echoed on EWTN) by invoking the age old maxim that the ends justify the means, but that is a utilitarian principle not a Catholic one. Nor is the recourse to the category of intrinsic evil much help here. Lots of things are intrinsically evil including birth control and as I have pointed out before there is not a mayor nor a governor who does not sign a budget that funds some form of birth control policy.

Commentators have tended to ignore the second sentence in the document’s bullet point on the conferral of honors: “They should not be given awards, honors or platforms which would suggest support for their actions.” Now, I thought Father Jenkins made it very clear, both in his initial announcement in March and at the commencement ceremony on Sunday, that Notre Dame was not honoring the President because of his positions on abortion and embryonic stem cell research but for his other notable accomplishments. The bishops may want to strike this sentence and say – do not honor these guys period. But, any fair-minded person would be wrong to fault Father Jenkins for violating this document when you read it in its entirety.

So, the bishops have their work cut out for themselves at San Antonio. I suspect that at the end of the day, the authority of the local bishop in such matters will, and should, be highlighted. As Archbishop Donald Wuerl of Washington, one of the most thoughtful and theologically sophisticated bishops in the country, wrote in his weekly column last week discussing this very document, “While everyone may not agree with how an individual bishop applies this principle for institutions within his own diocese, it, nonetheless, is the bishop’s call.” That may not make everyone happy – indeed, it won’t make everyone happy. But, the central role of the bishop as teacher within his diocese is more important than any political point. Yes, some bishops may turn their universities into intellectual ghettoes, allowed to invite no one with a differing or provocative position to campus. Others will follow James Joyce’s view: “Here comes everybody!” But, as Wuerl said, at the end of the day, in a hierarchical church, it’s the bishop’s call.

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