Engineered Stem Cells from Human Umbilical Cord Blood Eradicates Pancreatic Tumor

Tissue-specific stem cells called mesenchymal stem cells (MSCs) are a very efficient way to delivery new drugs to cancer sites. One of the reasons these cells do such a good job with cancers in that MSCs have a liking for tumors, and once MSCs are injected into a patient or laboratory animal with tumors, the MSCs make a “B-line” for the tumor and get cozy with it.

Interleukin-15 (IL-15) is a small protein synthesized by white blood cells in our bodies, and IL-15 has a demonstrated ability to stop tumors in their tracks. Unfortunately, IL-15 is broken down quickly once it is injected into the body and consequently, has to be given in very high quantities for it to work. At such high concentrations, IL-15 causes severe side effects, and therefore, it has not been pursued as an anti-tumor agent to the degree that it deserves.

To get around this problem, a Chinese group led by Kexing Fan from the International Joint Cancer Institute in Shanghai, China, genetically engineered MSCs isolated from human umbilical cord blood so that they expressed IL-15. When these engineered MSCs that expressed a mouse version of IL-15 were subjected to experimental verification, the expressed IL-15 activated white blood cells to divide just like native IL-15.

Next, Fan’s group used these souped-up cells to treat In mice afflicted with pancreatic tumors. Pancreatic cancer is an indiscriminate killer, since by the time it causes any symptoms, it is usually so advanced, that there is little to be done in order to treat it. Thus new strategies to treat this yep of cancer are eagerly being sought. Systemic administration of IL-15-expressing MSCs significantly inhibited tumor growth and prolonged the survival of tumor-bearing mice. The tumors of these mice showed extensive cell death, and other types of immune cells known to fight tumor cells (NK and T cells) had also accumulated around the tumor. Other experiments confirmed that the injected MSCs did indeed migrate toward the tumors and secrete IL-15 at the site of the tumors.

Interestingly, those mice that were cured from the pancreatic tumors, appeared to have a kind of resistance of these tumors. Namely, when Fan and his colleagues tried to reintroduce the same tumor cells back into the cured mice, the tumor cells would not grow. Thus the engineered MSCs not only tuned the immune system against the tumor, but they effectively vaccinated the mice against it as well.

Overall, these data seem to support the use of IL-15-producing MSCs as an innovative strategy for the treatment of pancreatic tumors.

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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).

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