Regular Stem Cell Transplants Extend Life in Normal Rats

Researchers here demonstrate extended life spans in rats as a result of life-long regular transplantation of stem cells. The specific mechanisms are unknown, but the researchers suggest that the proximate causes involve altered levels of various signal molecules leading to better operation and maintenance of native cells and tissues. Given that one study can't measure everything of interest, this should probably be taken as a preliminary set of suppositions, though reasonable given what is known of stem cell therapies at this point. Following on from this work it is definitely the case that more life span studies should take place for stem cell treatments.

Aging brings about the progressive decline in cognitive function and physical activity, along with losses of stem cell population and function. Although transplantation of muscle-derived stem/progenitor cells extended the health span and life span of progeria mice, such effects in normal animals were not confirmed.

Human amniotic membrane-derived mesenchymal stem cells (AMMSCs) or adipose tissue-derived mesenchymal stem cells (ADMSCs) were intravenously transplanted to 10-month-old male F344 rats once a month throughout their lives. Transplantation of AMMSCs and ADMSCs improved cognitive and physical functions of naturally aging rats, extending life span by 23.4% and 31.3%, respectively. The stem cell therapy increased the concentration of acetylcholine and recovered neurotrophic factors in the brain and muscles, leading to restoration of microtubule-associated protein 2, cholinergic and dopaminergic nervous systems, microvessels, muscle mass, and antioxidative capacity.

The results indicate that repeated transplantation of AMMSCs and ADMSCs elongate both health span and life span, which could be a starting point for antiaging or rejuvenation effects of allogeneic or autologous stem cells with minimum immune rejection.

Link: http://dx.doi.org/10.5966/sctm.2015-0011

Comments

I wouldn't have expected that just administering MSCs intravenously would extend lifespan in rat models. It would be interesting to see what effect on the endpoints about administering those stem cells in a Rhesus monkey would achieve (as measuring any lifespan increase would take too long).

Posted by: Jim at August 31st, 2015 5:34 PM

It does not surprise me, it is well known that MSCs have regenerative properties and even culture medium that MSCs have been in sans the cells do too. An MD friend of mine has used MSCs to treat ALD with reasonable levels of success, the MSCs and the culture medium have a paracrine effect. Makes me think one could harvest MSCs from adipose fat, regenerate them ex-vivo then "milk" them for paracrine factors.

I was reading a paper today that talks about MSCs strangely enough:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2667788/

and a Conboy paper relating to hESCs:

hESC-secreted proteins can be enriched for multiple regenerative therapies by heparin-binding. - PubMed - NCBI

The MD I know wants to use MSCs to treat Parkinson's in fact with this paracrine effect to stimulate regeneration and production of H factor to clear plaque.

Posted by: Steve H at September 1st, 2015 4:33 AM

The problem with MSCs is they seem to become less effective at regenerating the older the donor which if you take ADMSCs to use elsewhere in the body they kind of hit a brick wall in terms of usefulness.

Taking MSCs and modifying them ex-vivo is something the MD I know wants to test. It could be useful if the MSC were treated with gene therapy that can overcome the aged environments inhibitory effects for the tissue in question.

This brick wall is discussed here:

http://www.stemcellres.com/content/pdf/s13287-015-0127-9.pdf

Posted by: Steve H at September 1st, 2015 6:27 AM

If Michael is lurking around. Can we use ADMSCs and ADMSC derived culture as a therapy to help stabilize the system and help restore the signalling environment?

There have been numerous experiments showing their potential can we use this as part of SENS strategy?

Posted by: Steve H at September 2nd, 2015 2:21 AM

Hi Steve,

SENS is a damage-repair approach: interventions that act directly on the signaling environment (through drugs, or parabiosis, or "para-parabiosis," or in this case the paracrine effects of non-parenchymal cells) may have some acute benefits, but are ultimately unsustainable because of the very nature of the degenerative aging process. They leave the underlying damage unresolved and continuing to accumulate, and require ongoing interference in metabolic processes, which will inevitably lead to deleterious side-effects as they counteract the (mal)adaptive changes that cells and tissues adopt to sustain function in the face of accumulating damage. We're not going to find ways to antagonize the senescence-associated secretory phenotype: we're going to ablate the cells that are causing it, and replace them with functioning new ones. We're not going to try to damp down the oxidative stress induced systemically when cells harboring mitochondrial deletion mutations change their energy-production mode to survive: we're going to obviate their need to export reducing equivalents by replacing the missing components of the electron transport chain, thereby restoring normal energy production. Etc.

The reason SENS Research Foundation is funding heterochronic plasma exchange and related research in Dr. Conboy's lab is that hers and similar studies (such as this one, or bone marrow and similar nonparenchymal stem cell transplants after an induced heart attack) is not to develop therapeutics. It is to give us clues about:

(a) factors that might be used transiently as adjuvants to specific rejuvenation biotechnologies in order to ensure that they "take" (e.g., hypothetically, TGF-β inhibitors during the initial rebuilding of skeletal muscle using satellite cells);

(b) the effects we will get "for free" once the original damage is repaired, and thus for which we need not worry about seeking a direct solution; and therefore sometimes

(c) which damage-repair therapeutics to prioritize (in R&D or in clinical protocols as part of administering a comprehensive suite of rejuvenation biotechnologies) in order to bootstrap the successful clinical use of the succeeding therapies in the protocol.

Posted by: Michael at September 2nd, 2015 3:48 PM

It's not actually that MSC transplantation extended normal lifespan in these animals. While they used normal, healthy lab rats, the control animals were quite short-lived. The investigators used male F344 rats, which in the NIA's Biomarkers of Aging Program had average and median lifespans of 721 and 718 days (respectively), and 896 days as maximum LS; in this study, the mean and last-survivor max LS in the control group was just 604.6 and 700 d. The groups given the stem cells did live longer (AMMSC: 746.0 and 912 days; and ADMSC: 793.8 and 1033 days, respectively), but most of the difference just makes up for the miserably short-lived control group; there is a suggestion of a real effect of ADMSC, but we have no good control group and the study was underpowered and assigned 50% more animals to the ADMSC group to begin with (30, vs 20 in the others), and in an underpowered study like this you can wind up with a longer sole-survivor maximum lifespan by sheer dint of numbers.

Posted by: Michael at September 2nd, 2015 9:47 PM

Interesting thank you Michael.

What about therapeutics that for example can mediate removal of complement from neurons so they do not die and and regrowth of lost neurons? There is some promising data that stem cells for example can achieve this in Parkinson's and ALS. It obviously does not address the reason for that damage but is perhaps useful for those already suffering with the condition?

What can a gene therapy or Biotech company do to develop useful technology that complements the SENS approach?

Posted by: Steve H at September 3rd, 2015 2:06 AM

Also agree about the experimental protocol here it does make the results a bit less clear. I think there is some benefit here for sure but it needs repeating with a proper control.

Posted by: Steve H at September 3rd, 2015 5:35 AM

@Michael what about clearing the niche and importing fresh MSCs to replace them? This would remove the issue of the niche resisting engraftment with new cells.

Posted by: Steve H at September 4th, 2015 7:07 AM

Post a comment; thoughtful, considered opinions are valued. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.