Driven by increases in government research funding, advances in the treatment of chronic diseases through stem cell therapy and an overall spike in demand for cell-based products from leading biotechnology companies, the cell expansion industry will grow to $18.76 billion worldwide by the year 2021 at a compound annual growth rate of 17.6 per cent from 2016 to 2021, according to a new report by market research company MarketsandMarkets.
Regenerative medicines, cancer research and cell-based therapies are all expected to push the demand for available stem cells to new heights, with the human cells segment of the market forecasted to take up the largest share of the cell expansion market, the report points out.
“Increasing investments by companies for the development of cell-based therapies are driving the growth of this market,” says the report. “End users included in the cell expansion market are research institutes, biopharmaceutical and biotechnology companies, cell banks, and others.”
Cell expansion protocols have advanced rapidly during the past decade, but the process required to successfully generate new stem cells from a given starting population is still quite challenging, and with new research and therapeutic applications for stem cells literally being advanced on a daily basis, the future demand for cells is only expected to increase.
Canadian biotechnology companies are well-poised to be key players in the field of stem cell research and applications, thanks in part to a federal government that appears keen to create a stronger climate of innovation in the country.
NIH researchers develop clinical-grade stem cells
Researchers supported by the National Institutes of Health (NIH) has developed a clinical-grade stem cell line, which has the potential to accelerate the advance of new medical applications and cell-based therapies for millions of people suffering from such ailments as Alzheimer’s disease, Parkinson’s disease, spinal cord injury, diabetes, and muscular dystrophy. The stem cells were developed by isolating human umbilical cord blood cells following a healthy birth, and coaxing them back into a pluripotent state, or one in which they have the potential to develop into any cell type in the body. Cells developed in this manner are called induced pluripotent stem cells (iPSCs). With NIH support, these cells were manufactured by Lonza, Walkersville, Maryland, and described in a publication by Behnam Baghbaderani, Ph.D., and colleagues in Stem Cell Reports.
These clinical-grade stem cells are different from the more common laboratory-grade cells – those used in most scientific publications – because unlike laboratory-grade stem cells, clinical-grade stem cells can be used for clinical applications in humans. The distinctive feature of this cell line is that it was developed under current good manufacturing practices (cGMP), a set of stringent regulations enforced by the U.S. Food and Drug Administration which ensures each batch of cells produced will meet quality and safety standards required for potential clinical use. The NIH Common Fund’s Regenerative Medicine program supported the manufacturing of this cell line.
“The Common Fund aims to accelerate research progress by developing new tools and resources for the biomedical research community through strategic investments in high-impact research,” said James M. Anderson, director of the NIH Division of Program Coordination, Planning, and Strategic Initiatives, which houses the Common Fund. “Since meeting cGMP guidelines is very time-intensive and costly, providing access to clinical-grade stem cells removes a significant barrier in the development of cell-based therapies.”
Significant progress with stem cell therapy in mice is already underway. Researchers have reversed diabetic conditions in mice using iPSC-generated insulin-producing cells and have partially restored limb function in mice with spinal cord injuries. Translating these studies into humans is the next challenge, and by making clinical-grade stem cells available, NIH hopes to speed up the development of new stem cell therapies for patients.
The clinical-grade stem cells, as well as research-grade cells cultured from the same cell line, are available for order and will be stored and distributed by the National Institute of Neurological Disorders and Stroke (NINDS) Human Cell and Data Repository (NHCDR) (link is external) that is supported through a NINDS grant to RUCDR Infinite Biologics at Rutgers University, Piscataway, New Jersey. RUCDR also distributes laboratory-grade cell lines made by the NIH Regenerative Medicine Program.
Laboratory-grade cells can be used for research that lays the foundation for eventual use of clinical-grade cells, such as determining the conditions necessary to guide the iPSCs to become specific cell types like neurons, insulin-producing beta-cells, or heart cells.
“As part of our long-standing commitment to providing critical biospecimens of the highest quality to investigators around the world, we share the excitement of being able to provide access to this resource,” said Dr. Michael Sheldon, director of the Stem Cell Center at RUCDR. “The Regenerative Medicine Program’s laboratory-grade stem cells are frequently requested by researchers. Given the therapeutic potential of the cGMP clinical-grade stem cells we anticipate a strong demand from both the academic and corporate sectors.”
The Regenerative Medicine Program supported the manufacturing of the clinical-grade stem cell line as part of its mission to serve as a national resource for stem cell science to accelerate the development of new medical applications and cell-based therapies. Another avenue through which the Regenerative Medicine Program is fulfilling its mission is through the Stem Cell Translation Laboratory (SCTL) that is funded by the Common Fund and administered by the NIH’s National Center for Advancing Translational Sciences (NCATS). The aim of the SCTL is to remove barriers that currently impede the therapeutic application of iPSCs, which include the lack of highly reproducible and well-defined procedures required to generate, characterize and differentiate patient-specific iPSCs in a safe fashion for pre-clinical and clinical use. In parallel to developing an integrated stem cell research program within NCATS, the SCTL will soon be soliciting collaborations from the research community in order to address the most pressing impediments towards stem cell therapies.
The NIH Common Fund encourages collaboration and supports a series of exceptionally high-impact, trans-NIH programs. Common Fund programs are designed to pursue major opportunities and gaps in biomedical research that no single NIH Institute could tackle alone, but that the agency as a whole can address to make the biggest impact possible on the progress of medical research.
Rapid-response immune cells
Through the use of powerful genomic techniques, researchers at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) have found that the development of immune cells, called innate lymphoid cells (ILCs), gradually prepares these cells for rapid response to infection. This work, which appeared online recently in Cell, sheds light on the development and function of a cell type that is increasingly recognized as having an important role in the body’s immune defense. NIAMS is part of the National Institutes of Health.
“Up until now, researchers have focused on T cells--another type of immune cell,” said John J. O’Shea, M.D., scientific director of NIAMS and senior author of the paper. “ILCs are coming into the spotlight because they appear to have a critical role in defending the body’s barrier regions, such as the skin, lungs, and gut, where microbes must first pass to make their way into the body.”
Our immune system has two arms — innate and adaptive. ILCs are innate immune cells that respond quickly against pathogens at the first site of invasion. They release small molecules called cytokines that transmit signals to fight infection.
The adaptive immune response kicks in more slowly to build an army of cells that can target specific offending pathogens. T cells, especially helper T cells, are a key part of the adaptive immune system. They produce different cytokines depending upon the type of pathogen they are trying to combat.
The importance of T cells became apparent during the 1980’s with the emergence of HIV and AIDS. HIV attacks a certain class of T cells, destroying a person’s immune defences and leaving him or her susceptible to infection and cancer. Since that time, investigators around the world have identified the distinct functions of T cell subclasses, providing new insights into their roles in host defence and opportunities for novel therapeutic strategies.
ILCs have received less attention despite their critical role in mounting the innate immune response. Recent work has revealed that ILCs and T cells mirror each other in their subclasses, which are defined by the kinds of cytokines they produce. However, the relationships between the two types of cells have been unclear.
To determine what sets ILCs apart from T cells, Dr. O’Shea’s team looked to the foundation of a cell’s identity — its genetic information, which provides detailed instructions for how a cell functions. Part of what makes each cell type unique is its distinctive pattern of DNA structure and regulatory factors. The combination of a stretch of DNA and a set of regulatory factors can be thought of as a switch — it helps determine whether a gene is turned off (inactive) or on (active).
Inactive regions of DNA are twisted into tight coils, whereas active regions are open and accessible to the cellular machinery that reads the genetic information. The open portions of the genome include genes themselves, as well as many regions that contribute to the regulation of their activities (the switches). The areas of the genome and the factors that control whether or not the information is read, in total, are referred to as the cell’s regulome.
Working in mice, the researchers analysed regions of the genome that control the cytokine genes produced by both ILCs and T cells. They found that each subclass of ILCs is associated with a distinct pattern of accessible regions. These patterns can be viewed as a type of bar code for each subclass. Further experiments showed that ILCs acquire their bar codes in a stepwise manner over the course of cellular development.
Importantly, the analysis showed that the bar codes are in place in ILCs before they encounter infection. This open, accessible configuration surrounding the switches that control cytokine genes may be instrumental in enabling ILCs to rapidly launch an assault upon infection.
In contrast, the researchers found that many of the DNA regions controlling cytokine genes in the mice’s T cells are inaccessible and silenced prior to exposure to a pathogen. But upon infection, T cells adopted bar codes similar to those of their ILC counterparts. This result reflected earlier findings that ILC and T cell subclasses produce similar sets of cytokines, but also revealed differences in how the two cell types control the activities of these key immune response genes. While the regulatory landscapes of ILCs are primed for a quick defense upon infection, those of T cells are minimally prepared when the pathogen invades. Only following infection are modifications in the landscape made that enable T cells to launch their attack.
“ILCs and T cells appear very different, but in the end, the way they control key responses is amazingly similar,” said Han-Yu Shih, Ph.D., a post-doctoral fellow at NIAMS and first author of the paper. “ILCs were discovered less than a decade ago, but the parallels between them and T cells will enable us to more quickly understand how they work and to develop ways to enhance or inhibit their function in treating a variety of immune and inflammatory diseases.”
This work was supported by the NIAMS intramural research program under project number ZIA-AR041159. The National Institute of Allergy and Infectious Diseases and the Beltsville Human Nutrition Research Center also provided support for the study.
The mission of the NIAMS, a part of the US Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases.
Transplanted stem cells give rise to blood cells
A team of researchers led by scientists at St. Jude Children's Research Hospital is looking at ways to improve how blood-forming stem cells can be used for therapeutic interventions. The work has uncovered a group of genes that regulate how hematopoietic stem cells start to grow and thrive in mice. The function of many of these genes was previously unknown. Reconstitution of a robust blood-forming system is essential for recovery from many catastrophic diseases as well as from chemotherapy treatments. A report on this study appears today in the Journal of Experimental Medicine.
Hematopoietic stem cell transplantation is the only therapy that cures many catastrophic malignancies linked to bone marrow or immune system failure. However, generating sufficient quantities of viable stem cells for this type of intervention is immensely challenging. Despite efforts to increase the yield of blood-forming stem cells, the viability of these cells in culture remains a problem. As an alternative to this type of approach, St. Jude researchers are looking at ways to enhance how these rare but valuable stem cells take hold once transplanted into a new host.
"We recognized that one barrier to improving blood stem cell transplantation is a lack of understanding of how these blood-forming stem cells successfully grow in the challenged environment of transplant. So we set out to identify the genes that control this process," said Shannon McKinney-Freeman, Ph.D., assistant member in the St. Jude Department of Hematology and the study's corresponding author.
"Our hope is to decipher the critical molecular pathways that control the ability of these clinically valuable cells to transplant into a new host," added Per Holmfeldt, formerly a post-doctoral fellow at St. Jude and one of the study's authors.
According to the National Bone Marrow Registry, about 3,000 children require hematopoietic stem cell transplantation each year in the United States. Much of the mortality and morbidity linked to this type of transplantation is due to infection and other complications but could be addressed in some way by protocols that enhance the growth of new blood cells arising from transplanted stem cells.
After four years of work, a new screening method developed in mouse model systems turned up 17 genes that are novel regulators of hematopoietic stem cell transplantation. Thirteen of these genes had never before been linked to the biology of engraftment of blood-forming stem cells. Engraftment is when new blood-forming stem cells start to grow and produce healthy, mature blood cells.