Mesenchymal stem cells in organ transplantation
By Maria Frisch

Share this article:  

In October of 2012, the Mesenchymal Stem Cells Solid Organ Transplantation (MiSOT) Consortium met to review the current state of clinical data. In June, they released a position paper that reviewed the safety and efficacy of mesenchymal stem cells (MCS) as a therapeutic agent in solid organ transplantation. This article has been adapted from that position paper to present the clinically applicable highlights and to summarize what you need to know for your practice.

MSC are one of the most promising cell populations for cell-based immunomodulatory therapy in solid organ transplantation. While not officially classified, the International Society for Cell Therapy provides the most widely accepted definition of these cells: adherent cells with multilineage differentiation capacity, a CD73+, CD90+, CD105+, CD14-, CD34-, CD45- and HLA -DR - immunophenotype and the capacity to differentiate into osteoblasts, adipocytes and chondrocytes. Some samples may also contain stromal cells.

These multipotent cells possess immunomodulatory and regenerative capacities, with properties that make them ideal for use as cell therapeutic agents in the solid-organ transplantation. During the last two years, MSC have been applied to the clinical setting in several phase I trials and developments in ongoing or trials nearing initiation. To date, MSC administration in clinical transplantation has proven relatively safe and feasible. Indications of efficacy include:

preventing acute cellular rejection (due to control of lymphocytes, antibodies, etc. and tissue remodelling.)
reducing immunosuppressive regimens (through inhibition of T-cell proliferation, inhibition of dendritic cell maturation, and induction of regulatory T cells.)
inducing long-term stable graft function
reducing tubulitis and interstitial fibrosis/tubular atrophy in some patients

However, there are also several problems that need to be addressed before the use of MSC becomes clinically appropriate. These include:

• proper timing (pre, post, or during transplantation)
• concomitant immunosuppression (optimal drug selection)
• source (bone marrow, adipose tissue, cord blood or other human tissues)
• immunogenicity (economic and logistic implications)
• oncogenicity (no malignant maldifferentiation found, but researchers remain cautious)
• opportunistic infection (may increase susceptibility)
• regulatory (challenging to translate from bench to bedside within US and EU regulatory reqs)

Maria Frisch is a healthcare consultant and clinical research scientist. She received her medical training from St. George's Medical School and graduate training in public health from the University of Minnesota. She is founder and CEO of Wolters and Brown Consulting.