Rejuvenating Aged Stem Cells With a Fountain-Of-Youth Cocktail


Stem cell researchers from the laboratory of Ren-Ke Li at the University of Toronto have discovered a cocktail that can kick old, lagging stem cells in the backside and renew their regenerative capacities.

Donated bone marrow stem cells are transplanted into patients with leukemia, or diseases that compromise bone marrow function. Unfortunately, even though such therapies save hundreds to thousands of lives every year, some of these patients die or become horribly ill because the patient rejects some of the cells in the donated bone marrow. To reduce the risk of bone marrow rejection, stem cells treatments have used stem cells from the patient’s own body. Unfortunately, such a strategy is unusable in older patients, since their stem cell function has been vitiated by the ravages of age. If there is a way to beef up the stem cell function of an older patient, why then, this protocol would definitely be preferred.

Ren-Ke Li, professor in the Division of Cardiovascular Surgery and a member of the Institute for Biomaterials and Biomedical Engineering at the University of Toronto, Canada and his colleague Milica Radisic, an associate professor of chemical engineering have designed a unique micro-environment that allows heart tissue to grow from stem cells donated by elderly patients.

This micro-environment utilizes a porous scaffold made of collagen (the protein found in scar tissue), and embedded in this scaffold are two growth factors (vascular endothelial growth factor and basic fibroblast growth factor). Radisic and Li and their co-worked seeded these scaffolds with stem cells taken from younger (~50 years old) and older donors (~75 years old) and then used them to repair the left ventricles of rats with damaged hearts.

The scaffolds without growth factors and seeded with stem cells from older donors did not repair the hearts very well, but those scaffolds without growth factors and seeded with stem cells from younger donors did a good job of repairing the hearts. When the scaffolds impregnated with growth factors were seeded with stem cells from older donors, the patches did a much better job of repairing the hearts; they did as good a job of facilitating heart repair and those scaffolds seeded with stem cells from younger patients.

Patch Morphology 28 Days After Implantation In Vivo(A) Representative images of rat hearts show the outer border of the patches depicted by the yellow dotted line. (B) Patch area was quantified using computerized planimetry. The patch area increased in all groups from the original size of 39 mm2(red dotted line) at the time of SVR. Patch area in the Old group was significantly larger after implantation than that in the other groups. The addition of cytokines significantly prevented patch expansion. (C) Representative images of heart slices stained with Masson's trichrome. Arrows indicate patch thickness. (D) Patch thickness was quantified using computerized planimetry. The patches in the Old group were significantly thinner than patches in the Young and Young + GF groups. Cytokine enhancement did not significantly increase patch thickness for old or young cells. *p < 0.05, **p < 0.01 vs. Old; Old n = 5, Young n = 8, Old + GF n = 6, Young + GF n = 8. GF = growth factor.
Patch Morphology 28 Days After Implantation In Vivo(A) Representative images of rat hearts show the outer border of the patches depicted by the yellow dotted line. (B) Patch area was quantified using computerized planimetry. The patch area increased in all groups from the original size of 39 mm2(red dotted line) at the time of SVR. Patch area in the Old group was significantly larger after implantation than that in the other groups. The addition of cytokines significantly prevented patch expansion. (C) Representative images of heart slices stained with Masson’s trichrome. Arrows indicate patch thickness. (D) Patch thickness was quantified using computerized planimetry. The patches in the Old group were significantly thinner than patches in the Young and Young + GF groups. Cytokine enhancement did not significantly increase patch thickness for old or young cells. *p < 0.05, **p < 0.01 vs. Old; Old n = 5, Young n = 8, Old + GF n = 6, Young + GF n = 8. GF = growth factor.

When Li and his team tracked the molecular changes in the stem cells grown on the scaffolds, they found that these cells acted like younger stem cells. In Li’ words: “We saw certain aging factors turned off.” The levels of two molecules in particular, p16 and RGN were reduced in the older stem cells grown on the growth factor-containing scaffolds, which turned back the clock in these cells and returned them to a more robust and healthy state.

Li and Radisic hope to experiment with their micro-environment in order to make it as effective as possible. According to Li, “We can create much better tissues which can then be used to repair defects such as aneurysms.” Li also thinks that these cells could be used to repair the heart after a heart attack.

See Kai Kang, et al., Aged Human Cells Rejuvenated by Cytokine Enhancement of Biomaterials for Surgical Ventricular Restoration,” Journal of the American College of Cardiology 2012 60(21): 2237 DOI: 10.1016/j.jacc.2012.08.985.

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mburatov

Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).