Mesenchymal stem cells in skeletal muscle regeneration

Garza-Rodea, A.S. de la (2011)

Doctoral Thesis

Stem cell-based therapies represent promising approaches for the treatment of incurable diseases and tissue injury due to the capacity of these cells to self-renew and differentiate into specialized mature cells. Understanding the interaction of stem cells with the disease/injured environment and their contribution to the repair process by release of regeneration-promoting signals or by differentiation into the lost cell types is crucial for the advancement of their clinical application. This thesis focuses on one stem cell population, the mesenchymal stem cells (MSCs) from human and in particular on their role and utility in skeletal muscle regeneration. For this purpose, several in vivo tissue damage models were employed (i.e. cardiotoxin-induced injury, pressure ulcers, and subcutaneous implants of minced skeletal muscle). Most of the experiments were performed in immunocompromised mice (i.e. NOD/SCID) to avoid immunological rejection of the human cells. Furthermore, we described the downregulation of MHC class I protein expression on the surface of human MSCs by retroviral vectors encoding a herpesviral immunoevasin (i.e. the US11). This renders human MSCs vulnerable to NK cell recognition and cytolysis implies that multiple viral immune evasion proteins are likely required to make human MSCs non-immunogenic and thereby universally transplantable.

• Xenotransplantation
• Skeletal muscle regeneration
• Pressure ulcers
• NOD/SCID mice
• Human mesenchymal stem cells
• Herpes virus immune evasion proteins
• Experimental diabetes
• Decubitus
• Cell therapy

• All authors: Garza-Rodea, A.S. de la
• Supervisor: Valerio, D.
• Co-supervisor: Knaän-Shanzer, S.; Vries, A.A.F. de
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2011-09-28
• ISBN (print): 9789088913235
• Sponsorship: Harlan Laboratories