The thymus is an organ that sits over the top of the heart and it plays a pivotal role in the development of T-lymphocytes. The thymus is a very durable organ that can readily regenerate if it is injured. This regenerative ability is largely due to it high level of vascularization (lots of blood vessels). This vascularization is due to a robust population of resident mesenchymal stem cells that supports blood vessel formation in the damaged thymus. The process of blood vessel formation is called “angiogenesis.” The angiogenic potential of these thymus-based mesenchymal stem cells might hold excellent potential for regenerative therapies.
As it turns out, neonatal surgeries tend to generate thymus tissue that is usually thrown out as medical waste. Ming-Sing Si from Mott’s Children Hospital in Ann Arbor, Michigan and colleagues isolated mesenchymal stem cells from these surgically-derived neonatal thymuses and tested their ability to stimulate blood vessels in an experimental setting.
Discarded thymus tissue was obtained from the University of Michigan, and this tissue was minced, degraded with enzymes, and cultured. The mesenchymal stem cells (MSCs) moved from the thymus tissue onto the culture dishes. These thymus-based MSCs grew like gangbusters in culture and could be passaged over 30 times.
When these thymus-based MSCs were combined with human umbilical vein endothelial cells, within one day, the cells formed an extensive network of blood vessels.
Gene expression studies showed that culturing thymus MSCs with human umbilical vein endothelial cells (HUVECs) caused the HUVECs to express a variety of blood vessel-specific genes. These thymus-based MSCs were also able to induce blood vessels if the cells were wadded up into a ball (spheroids).
To top it all off, Si and others implanted thymus-based MSCs underneath the skin of nude mice. They used hydrogels with no cells, hydrogels plus HUVECs, hydrogels plus thymus-based MSCs, and hydrogels with thymus-based MSCs plus HUVECs. The control implants and the HUVEC implants showed no blood vessels. HUVECs make very good blood vessels, but they have to be directed to do so. Both the thymus-based MSCs and the MSCs plus HUVECs showed extensive integration into the host tissue with lots of blood vessels.
These MSCs show low expression of human leukocyte antigen class I, which, translated, means that these cells are unlikely to be recognized by the patient’s immune system. Therefore, these cells could be donated to patients whose resident MSCs are of poor quality or do not have enough of their own MSCs for therapeutic processes.
This paper shows that discarded neonatal thymus contains large numbers of resident MSCs that can be isolated and cultured by a standard explant method. These MSCs have all the characteristics of traditional MSCs, but have more robust growth characteristics in culture. These thymus MSCs also possess outstanding proangiogenesis qualities that should be further tested and considered as promoters of tissue and organ regeneration in tissue engineering strategies.