Pluripotent Stem Cells Are There to Be Found in Adult Tissues

One of the emerging themes over the past few years of stem cell research is that various forms of pluripotent stem cell can be found in adult tissues. Pluripotency in a stem cell is the ability to differentiate to form lineages of any cell type in the body. The well known types of adult stem cell that researchers have cataloged over the past few decades are only multipotent, meaning that they are limited in the type of cell lineages they can create. A multipotent stem cell supports a particular tissue type made up of a few types of cell.

Why does this matter? It's all about the efficiency and cost of research and development of regenerative therapies based on the use of stem cells. If researchers must locate and understand specific multipotent cell populations in order to regenerate a specific type of tissue, then a great deal of work remains on the way to a comprehensive regenerative medicine toolkit. Every type of multipotent stem cell has its own distinct behaviors and mechanisms, and requires a different environment to grow in useful numbers outside the body. Discovering how to make use of any specific type of multipotent stem cell has proven to be a slow process of trial, error, and educated guesswork. On top of that, researchers haven't yet reliably identified multipotent stem cells in all types of tissue, and most of the known populations are far from well understood. There are hundreds of cell types in the human body, and much left to accomplish.

If researchers can obtain a reliable, low-cost source of pluripotent stem cells, however, then that single resource can be used to generate any type of cell you want, starting from the same shared baseline. It greatly cuts down the complexity and work required to move forward with regenerative medicine. This is why the research community is so focused on embryonic stem cells and the reprogramming of ordinary cells into induced pluripotent stem cells. Pluripotent cells obtained directly from an patient's tissues, especially those that are easily accessed such as skin and fat, may be even better than induced pluripotent stem cells in terms of cost-effectiveness. Such a resource cuts out yet another step in the process of obtaining broadly useful patient-matched cells for research and regenerative therapies.

In recent years a few research groups have claimed the identification of pluripotent stem cells in adult tissue. They have given the cells various different names, such as very small embryonic-like stem cells (VSELs), but they might all be talking about the same thing - or they might not. Biology is always more complex than you think it is. Why shouldn't there be all sorts of variously potent cell types hiding away in our bodies in larger or smaller numbers?

Here is an open access publication from another research group to have isolated pluripotent stem cells in adult tissue. From a long term perspective, the more of this that happens the better, I think. It suggests that over the next decade or two regenerative research will move more rapidly than would otherwise have been the case:

Awakened by Cellular Stress: Isolation and Characterization of a Novel Population of Pluripotent Stem Cells Derived from Human Adipose Tissue

Recently, a new stem cell population has been isolated from mesenchymal tissues such as human skin fibroblasts and bone marrow stromal cells under cellular stress conditions. These cells, termed Multilineage Differentiating Stress-Enduring (Muse) Cells, are of mesenchymal stem cell origin and comprise 1-3% of the entire cell population. Muse cells exhibit characteristics of both mesenchymal and pluripotent stem cells. They are double positive for CD105, a mesenchymal stem cell marker, and stage specific embryonic antigen-3 (SSEA3), well known for the characterization of undifferentiated human embryonic stem cells (ES) from bone marrow aspirates or from cultured mesenchymal cells such as bone marrow stromal cells and dermal fibroblasts. They express pluripotency markers including [those used to create induced pluripotent stem cells], differentiate into cells of ectodermal, endodermal, and mesodermal lineages both in vitro and in vivo, and have the ability to self-renew.

Advantageously, Muse cells do not appear to undergo tumorigenic proliferation, and therefore would not be prone to produce teratomas in vivo, nor do they induce immuno-rejection in the host upon autologous transplantation. In addition, Muse cells are shown to home into the damage site in vivo and spontaneously differentiate into tissue specific cells according to the microenvironment to contribute to tissue regeneration when infused into the blood stream. Therefore, they exhibit the potential to make critical contributions to tissue regeneration in the absence of restrictions attributed to the difficult extraction of bone marrow stromal cells and human skin fibroblasts, and time-consuming purification methods such as cell sorting. In order to increase the viability of Muse cells as a source of tissue regeneration, a more accessible supply must be utilized.

Harvesting human adipose tissue by lipoaspiration is a safe and non-invasive procedure, and hundreds of millions of cells can be isolated from 1-2 liters of lipoaspirate material. Therefore, adipose tissue could prove the ideal source for Muse cell isolation as opposed to bone marrow or dermis. Using lipoaspirate material, we developed a novel methodology for the isolation of a population of human Muse cells under severe cellular stress conditions (long term incubation with proteolytic enzyme, 4°C, serum deprivation, and hypoxia). Purification of human Muse cells derived from adipose tissue (Muse-ATs) does not require the use of cell sorting, magnetic beads or special devices.


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