What is a Stem Cell?
Our genome is not in a static state and although our genotype strongly influences resulting phenotype, there are many differences in gene function and expression that cannot be attributed to changes or differences in DNA sequence alone.
Stem cells are undifferentiated cells, unique in both their proliferative capacity and ability to specialize into different cell types. The majority of cells that make up the human body have a specific function and lifespan and do not have the capacity to renew. In contrast, stem cells are able to divide and produce copies, replicating many times and serving as a biological repair system for the body, forming the basis of normal growth and development. In addition to their self-renewal properties, stem cells can differentiate to become more specific and specialized cell types. The classification of stem cells can be based upon their differentiating potential:
- Totipotent – capable of forming any human cell including placenta and giving rise to an entire functioning organism
- Pluripotent – capable of forming any human cell, except placenta, thus cannot give rise to an entire functioning organism
- Multipotent – capable of forming a limited range of human cells, usually within a specific tissue type
- Unipotent – capable of forming human cells along only one lineage
Stem cells can also be classified based on their origin and are present in both the embryo (embryonic stem cells) and adult (adult stem cells). Embryonic stem cells are derived from one of the earliest stages of development, thus they are pluripotent and can give rise to all human cell types. Adult stem cells are undifferentiated cells found within differentiated tissue, they are multipotent and can renew and become specialized to form any of the cell types of the tissue of origin. There are many different types of adult stem cell including:
- Mesenchymal – differentiate to form skin, muscle, bone, fat, cartilage, tendon and ligaments
- Hematopoietic – differentiate to form red and white blood cells as well as platelets
- Neural – differentiate to form cells within the nervous system
All adult stem cells are considered multi- or uni-potent, however recent advances in stem cell research have enabled adult stem cells to be re-programmed to become embryonic cell-like, expressing genes that define and maintain the same properties as embryonic cells. These induced pluripotent stem cells have been shown in research settings to be capable of generating cells characteristic of all three germ lines and are currently being used in drug development, disease modelling, and are hopeful candidates in the field of transplantation medicine.
Stem Cell Research Areas
Stem cell researchers are interested in understanding the unique properties of stem cells, the drivers behind differentiation and self-renewal, as well as practical and therapeutic applications of stem cells in medicine.
The range of cloning and molecular interrogation products offered by Meridian covers a full suite of tools to assist efforts towards better understanding of stem cells and their unique properties. ISO 13485 manufacturing standards also supports seamless transition into therapeutic applications.
Understanding Stem Cell Development and Regulators of Potency
What are the properties within a stem cell that allow for numerous cycles of self-renewal? How does a stem cell remain undifferentiated? What are the factors that induce a pluripotent cell towards differentiation into the many hundreds of different cell types within the human body?
These are just some of the questions researchers are interested in understanding to shed light on the unique properties of stem cells, to understand how an embryo develops, or how hematopoietic stem cells balance self-renewal and the provision of differentiated progenitors for the maintenance of the blood system throughout life. Identifying the molecular cues that regulate stem cell systems, as well as the microenvironments that contribute the various triggers and maintenance systems, are key to gaining greater understanding of the unique properties of stem cells.
Induced Pluripotent Stem Cells
Pluripotent stem cells offer limitless possibilities for understanding human development and tissue formation, as well as the opportunity to model diseases and understand disease mechanisms, with ultimate aims towards cell therapy and regenerative medicine.
For many years embryonic stem (ES) cells were the sole source of pluripotent cells - carrying the weight and complication of associated ethical issues, the availability and utility of ES cells was ultimately limited. It was the Nobel-prize winning breakthrough from Takahashi and Yamanaka in 2006 that led to the identification of four important reprogramming factors that enabled generation of induced pluripotent stem cells (iPSCs) from previously differentiated somatic cells. From a simple skin biopsy or blood sample iPSCs can now be generated, offering genetically matched pluripotent cells for virtually any patient – not surprisingly, there is excitement around the potential of this field for understanding disease mechanisms and development of new treatment options. There are still many hurdles and details to understand and overcome, including the molecular characterization of iPSCs and whether they are indeed equivalent to ES cells – evidence indicates differences in efficacy of differentiation as well as DNA methylation patterns – plus identifying effective protocols to achieve appropriate and reproducible differentiation is also proving to be a challenge.
Cancer Stem Cells
Given their key role in so many important cellular functions, it stands to reason that aberrant epigenetic processes have been identified in many cancers, as well as other disease states. Hyper-methylation of CpG islands has been identified in a range of cancers resulting in subsequent silencing of tumor suppressor genes, DNA repair genes or other processes important to normal cell growth.
Through investigations into cancer metastases, disease recurrence, and acquired resistance to therapy, researchers have uncovered an enormous level of intratumoral heterogeneity, most likely due to a combination of genetic mutations and interactions with the tumor microenvironment, as well as the presence of what is now known as cancer stem cells (CSCs). Similar to normal stem cells, CSCs have self-renewal properties, however the strict regulations surrounding differentiation appear to be deregulated, resulting in continuous expansion and production of aberrant progeny – CSCs form tumors in healthy animals when transplanted, where normal stem cells do not. CSCs have now been identified in a broad range of blood and solid tissue tumors, including leukaemia, breast and brain cancers. While CSCs appear to represent a very small percentage of the tumor cell population, their existence has been used to explain how cancer cells are able to proliferate and acquire all the necessary mutations for cancer development, as well as the recurrent nature of many tumors, as CSCs appear to survive many cancer therapeutic efforts. Understanding CSCs and how they drive cancer development, as well as the mechanisms for how cancer patients acquire CSCs, form a major part of cancer research today.
Therapeutic Usage of Stem Cells
Stem cells have been referred to as an “Aladdin’s Lamp” with rich promise to cure many diseases, however the current reality is far from this ideal.
Efforts continue towards a better understanding of stem cell characteristics in order to harness this potential in the therapeutic realm. Today, stem cells are being used to produce differentiated cell lines for drug testing, previously only possible on animal models. Knowledge of the signalling mechanisms that control specific differentiation is still limited, and much more work can be done in this area to improve reproducibility and increase the range of available differentiated cell types. Harvesting of hematopoietic stem cells (HSCs) from bone marrow and more recently from circulating blood, has been used to treat blood cancer patients and replenish blood components after chemotherapy rounds.
Perhaps the most exciting potential for stem cell therapy lies in the generation of new cells and tissues to replace diseased or ailing counterparts. Known as cell-based therapy, this treatment is being looked at to regenerate spinal cord damage, brain injury and heart disease. With the advent of induced pluripotent stem cells, this approach to regenerative medicine is looking even more promising. From cloning and vector reagents, PCR and real-time PCR kits or individual components, sample preparation, sequencing and even whole assay design services, Meridian is ready with a full suite of tools to support the growing spectrum of stem cell research and application advances.