by Caitlin Smith
Removing cells from an adult, changing them into another cell type, and reintroducing them back into the adult who made them (with healing consequences)—it sounds like the plot of a medical sci-fi thriller, but today it is reality. Improvements in cell harvesting, passaging, and induction are rapidly pushing adult stem cells to the fore. Also, adult stem cells pose less of an ethical dilemma than embryonic stem cells. “Another exciting new development is the improvement in the yield of recovery of adult stem cells from various organs and the ability to grow them for several passages and expand them to large numbers without compromising their potential to differentiate,” says Mahendra Rao, Life Technologies’ VP of research for stem cells and regenerative medicine. “These developments are helping bring the power of adult stem cells to therapy and research.”
Telling what’s what
The challenges of characterizing adult stem cells (ASCs) are made easier by Novus Biologicals, which offers a range of primary antibodies, some labeled with enzyme or fluorochromes. Novus also sells growth factors or cytokines such as their NovActive® proteins. Mark Parker, senior scientist and head of product development at Novus, says that researchers working with adult stem cells need “a complete profiling system to isolate and differentiate multipotent [adult stem cells]. Researchers are attempting to identify more specific markers for ASCs from various cell lineages and this is a necessary step to further advance the adult stem cell field.”
Life Technologies offers a range of products for different cell types, such as mesenchymal stem cells (MSCs), hematopoietic cells, and neural stem cells. Their new tools include serum-free and xeno-free media for MSC culture, such as StemPro® MSC SFM, StemPro® MSC SFM XF, and CellStart®, as well as media to culture neural stem and progenitor cells, such as StemPro® NSC SFM, StemPro® Neural supplement. “We are the only company that manufactures all of its culture components GMP and the only one that designs its products to be compatible with the FDA's 510K filing requirements,” notes Rao. “These are critical requirements for reagents that are approved by the FDA for use in cell therapy, and this allows investigators who are moving from the bench to bedside to save valuable time.”
Additional tools for MSCs are offered by Vitro Biopharma, whose MSC lines claim a longer continuous expansion (at least 14 passages; about 50 population doublings) than most. They also sell MSCs with green or red fluorescent cell membranes. “These products are valuable tools in studies of tracking of adult MSCs to specific cellular targets, which is an important property of stem cells’ underlying therapeutic efficacy,” says James Musick, president and CEO of Vitro Biopharma. “For example, human MSCs are known to specifically migrate to cancer stem cells, and this cell-specific tropism has led to targeted delivery of cancer therapeutic drugs. Our initial studies of these products also indicate transfer of fluorescent label from MSCs to differentiated structures arising from these cells.”
Harvesting adult stem cells of interest
Harvesting adult stem cells for use in therapeutics is beginning to see some technological help. “If the treatment for acute myocardial infarction becomes the administration of bone marrow-derived stem cells in the cardiac catheterization laboratory, then the time required to harvest bone marrow, separate it from bone chips and other debris, concentrate the cells by centrifugation, and prepare them for delivery, are steps that predispose the patient to cell preparation-dependent delays in receiving the treatment and a risk of product contamination associated with cell preparation steps,” says Jerry Ortolano, Pall Corporation’s senior VP for scientific affairs and cell therapy field applications. Pall’s Purecell™ Select is a filtering cell harvest system that enriches mononuclear cells (MNCs) from blood, bone marrow, cord blood, or fat tissue; within the MNC population is found progenitor cells used in tissue repair. “In contrast to most other methods requiring the use of a centrifuge for the separation of MNCs using a Ficoll density gradient, the Purecell™ Select is a remarkably simple, functionally closed system,” says Ortolano. “The platform is intended for smooth transition from bench-to-bedside with processing of blood into enriched MNCs in less than 15 minutes.”
Another tool to speed stem cell research is StemCell Technologies’ MethoCult® Express, a methylcellulose-based medium designed to accelerate the proliferation of hematopoietic progenitors, and the formation of colonies in colony-forming cell (CFC) assays. “The CFC assay is widely used in cord blood banks and transplantation labs, and it has been found to be the best predictor of neutrophil and platelet engraftment and overall survival after transplantation,” says Kenneth To, product manager for hematology at StemCell Technologies. MethoCult® Express gives CFC results in seven versus 14 days.
The dawn of adult stem cell therapeutics
An exciting implication for adult stem cells is the possibility of therapeutics. “There are more than 85 clinical trials with adult stem cells, and the field has exploded with the discovery of easy-to-harvest sources,” says Rao. “Cord blood and [MSCs] are among the forefront of this effort. In addition, the possibility of reprogramming cells to form progenitors that are currently hard to obtain directly from tissue opens up a whole new set of opportunities in adult stem cells.”
Many hope that induced pluripotent stem (iPS) cells will also lead to therapeutic opportunities. “Given that iPS cells may be generated without transfection with foreign DNA, this technology may provide a basis for widespread use of personalized, autologous stem cell transplants for medical applications,” says Musick. “This may usher in revolutionary changes to medicine by allowing use of a patient’s own cells to treat a variety of conditions including degenerative diseases and cancer.”
Aastrom Biosciences develops autologous cell products for repairing human tissues. Their Tissue Repair Cell technology uses the patient’s own bone marrow cells to treat diseases, focusing on cardiac and vascular tissue regeneration. They use a mixture of stem and early progenitor cells cultured from bone marrow. “In the TRC-based products, stem and early progenitor cells are substantially expanded, several-fold for endothelial progenitor cells and up to 400-fold for the mesenchymal stem cells,” says Elmar Burchardt, VP of medical affairs at Aastrom Biosciences. “However, the overall number of cells in the final product is not higher than the initial number of cells going into the system. This is due to loss of the mature cells, such as blood constituents, during the manufacturing process.”
Lifeline Cell Technology, a subsidiary of International Stem Cell Technology, is developing a stroke model using neural stem cells from Arctic ground squirrels. The cells can proliferate in low oxygen and low glucose environments, making them useful test systems for therapeutics or for transplantation into rodent models. Lifeline is also trying to create islet cells from parthenogenic stem cells; this autologous approach might not work if the patient’s immune cells destroy the new islet cells as occurs in some forms of diabetes. Another exciting future direction is “transdifferentiation,” in which the re-expression of developmental regulators in vivo changes one cell type into another.
Amid the glimmer of productive research with adult stem cells lies a caveat explained by Jeffrey Janus, senior VP of operations at International Stem Cell, and president and CEO of Lifeline Cell Technology. “I think the biggest challenge to adult [stem] cell research ... is that creating an adequate and permanent source of cells that are identical in function will always be an issue for any kind of broad-based treatment based on adult cells,” he cautions. “This does not mean that adult cells are not very valuable. The challenge may be whether, once a cure is developed, a consistent and robust source of cells that are functionally equivalent to those used in the FDA trials can be sustained and produced in the quantities needed.”