Anyone who follows popular science news will have noticed that mesenchymal stem cells (MSCs) have gained traction in recent years. Alleviating chronic back pain, enabling stroke sufferers to walk again, manmade tracheas and a cure for Crohn’s disease – these are just some of the potential applications for MSCs that have made the news.
But what are MSCs and what is all the fuss about?
Mesenchymal Stem Cells at First Glance
MSCs belong to a heterogeneous group of multipotent stromal cells that are found in diverse tissue types e.g., the umbilical cord, amniotic fluid, bone marrow, adipose tissue, and peripheral blood. MSCs have the capacity to self-generate and differentiate into multiple distinct cell types e.g., osteoblasts, adipocytes, and chondrocytes. Depending on their external and tissue environment, MSCs exhibit distinct surface marker and gene expression profiles and morphologies. This explains why MSCs display donor-specific and organ-specific biomarker expression patterns, an important aspect for research and therapeutic development purposes.
Because they are easy to harvest from various adult tissue types, are multipotent, and exhibit an impressive capacity for self-renewal (i.e. growth without differentiation), MSCs have become an attractive tool within regenerative medicine, to artificially reconstruct and repair human tissues or organs which have been previously damaged following injury or disease. Their inherent immunosuppressive and anti-inflammatory properties also makes MSCs an ideal target for immunomodulation and anti-inflammatory therapies.
Although MSCs are not the only stem cells with huge therapeutic potential, they are often favored over the use of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), mainly due to ethical issues and concerns about genomic stability, respectively.
To date, MSCs have been investigated for their potential in a wide range of diseases and conditions, such as: multiple sclerosis (MS), chronic obstructive pulmonary disease, bone lesions, heart attack, inflammatory bowel diseases, and autoimmune diseases (e.g., psoriasis), to name a few.
Mesenchymal Stem Cell Transplants
Although it is possible to medically stimulate MSC differentiation and expansion in vivo, the efficiency of this approach is low, and the vast majority of therapeutic attempts with MSCs involve transplantation of a patient’s own MSCs after culture and expansion with a laboratory.
A typical MSC transplant occurs as follows:
- MSCs are isolated from the bone marrow of the patient (often from the hip bone)
- The isolated cells are cultured in growth medium under controlled laboratory conditions, where they expand (increase in numbers) and mature. This step is often the longest, and may take several weeks, and the desired cell type can be obtained by influencing the isolated MSCs in 3 distinct ways:
- Varying the density of cells in the growth medium
- Changing the conditions of the medium during the expansion step
- Adding hormones or other additives to specifically stimulate the differentiation of the desired cell type
- Expanded MSCs are then harvested and reintroduced into the patient’s body either via intravenous (IV) or intrathecally (lumbar puncture) injection.
Roadblocks to MSC Therapy
Despite the obvious potential for MSCs in regenerative medicine, most of what we know about their clinical potential and challenges comes from the MS field. The first clinical trial with MSCs were conducted in the mid-90s and there are currently around MSC-based 800 clinical trials listed in the US National Institutes of Health clinical trials database.
Realizing the therapeutic potential of MSCs is both a complicated and challenging goal, and disappointingly, no investigative MSC-based therapy to date has yielded consistent results. One significant roadblock to standardized MSC therapies is the fact that injected MSCs demonstrate limited survival in recipient tissue. These challenges further illustrate the need to understand donor-specific properties of MSCs and how different donor-derived MSCs behave ex vivo. Ultimately, what we learn will contribute to the success of new therapeutic developments.
New Research Tools for MSCs
Tempo-iMSC are human iPS-derived mesenchymal stem cells. Tempo-iMSCTM express cell surface markers such as CD73, CD90, CD166, and CD105, in addition to Oct4 and Nanog. This biomarker profile is predictive and useful for long-term cell culture and maintenance of MSC identity. MSCs have immunomodulatory features, secrete cytokines and immune-receptors that regulate the microenvironment in the host tissue, and they have multi-lineage potentials for a variety of cell types. MSCs can be used in a variety of screening applications, from screening biologics and small molecules to siRNAs. Their self-renewal capacity makes them readily scalable to accommodate large or high-throughput assays.
Are you working with MSCs in regenerative medicine? What are your biggest challenges?
Article by Karen O’Hanlon Cohrt PhD. Contact Karen at firstname.lastname@example.org.
Karen O’Hanlon Cohrt is a Science Writer with a PhD in biotechnology from Maynooth University, Ireland (2011). After her PhD, Karen moved to Denmark and held postdoctoral positions in mycology and later in human cell cycle regulation, before moving to the world of drug discovery. Her broad research background provides the technical know-how to support scientists in diverse areas, and this in combination with her passion for writing helps her to keep abreast of exciting research developments as they unfold. Follow Karen on Twitter @KarenOHCohrt. Karen has been a science writer since 2014; you can find her other work on her portfolio.