Mesenchymal Stem Cell Research

Using MSCs in research and treatments creates relatively little controversy and is normally considered safe in terms of a reduced risk of graft versus host disease as an autologous stem cell transplant is often possible. Patients undergoing chemotherapy or radiation therapy for cancer may have their own stem cells harvested from the bone marrow prior to myeloablation. Haematopoietic stem cells are also likely to be taken from the bone marrow in order to repopulate the body’s blood- and immune-forming system following the cancer treatment. Nerve cells, adipocytes, and liver and pancreatic cells have also been formed from MSCs making them an area of immense interest for stem cell researchers.

Difficulties of Mesenchymal Stem Cell Research

One of the difficulties with MSCs is in identifying them categorically. The standard test is the cells’ ability to differentiate into osteoblasts, chondrocytes, and adipocytes, as well as some neural cell types. This differentiation appears to be subtly affected by the chemical, and mechanical stimuli applied to the MSCs as well as the individuals from whom the cells are sourced. It is thought that the potency of the cells dissipates with age, as does their capacity to proliferate at the same rate as when young. This may be due to a decreased number of stem cells or a change in the cells themselves.

A mesenchymal stem cell (MSC) niche showing blood vessel (BV) interaction with differentiated cells (DC), signalling molecules, and surface receptors (Kolf et al, 2007).

Mesenchymal Stem Cells Slow and Scarce

Another problem encountered by those looking at using MSCs therapeutically is their relatively low numbers and slow activity. The necessity of culturing them in the laboratory prior to transplantation makes this process much slower than is desirable for patients hoping to start treatment after stem cell harvesting. Culturing the MSCs can however, cause them to differentiate prematurely and a number of researchers are investigating ways to culture the stem cells without biasing future differentiation that could reduce optimal usability. Biocompatible scaffolds, growth factors, and genetic modifications all hold promise for improving the opportunities of MSCs in therapeutic stem cell treatments. A study published in early 2011 showed that FGF-2 plays a major role in the differentiation of the mesoderm’s cells to MSCs and haematopoietic stem cells with potential application for controlling embryonic stem cells’ direction of differentiation (Slukvin, 2011).

Clinical Trials for Mesenchymal Stem Cell Research

The clinical trials involving mesenchymal stem cells that are either currently recruiting or nearing the recruitment stage reveals a variety of different possible applications for MSCs. Trials investigating conditions as diverse as ulcerative colitis, type 1 diabetes mellitus, multiple sclerosis, cirrhosis, cardiomyopathy, critical limb ischaemia and many others are listed at clinicaltrials.gov and offer hope to patient looking for novel treatment for their disease. With the vast number of trials in humans, and the possibility of donor mesenchymal stem cells not having to be an exact match to a patient due to various immunomodulatory effects, amongst other things, there is a possibility that mesenchymal stem cell products may be developed as off-the-shelf treatments in the coming years.

References

Slukvin II, Vodyanik M., Endothelial origin of mesenchymal stem cells, Cell Cycle. 2011 May 1;10(9). [Epub ahead of print]

Sessarego N, Parodi A, Podestà M, Benvenuto F, Mogni M, Raviolo V, Lituania M, Kunkl A, Ferlazzo G, Bricarelli FD, Uccelli A,Frassoni F., Multipotent mesenchymal stromal cells from amniotic fluid: solid perspectives for clinical application, Haematologica. 2008 Mar;93(3):339-46. Epub 2008 Feb 11.