Diaphragms grown in lab from mesenchymal stem cells and a 3D scaffold
Multidisciplinary team grows rat diaphragm tissue from a mix of mesenchymal stem cells and decellularized diaphragmatic tissue that regrows with the same complex mechanical properties of diaphragm muscle upon transplantation.
The diaphragm is a sheet of muscle continuously contracting and relaxing to allow breathing, and also aids swallowing and acts as a barrier between the chest cavity and abdomen. Malformations or holes in the diaphragm are found in 1 in 2500 infants and can cause severe, often fatal, symptoms. Injuries or malformations are currently treated with an artificial surgical patch, but defects can still recur and this treatment method lacks growth potential and restored functionality. A tissue-engineered diaphragm could improve surgical outcomes for patients with congenital or acquired disorders.
Researchers in Sweden, Russia and the USA including Paolo Macchiarini from the Karolinska Institutet, Doris Taylor from the Texas Heart Institute and Mark Holterman from the University of Illinois College of Medicine in Peoria have successfully engineered diaphragm tissue in rats using a decellularized diaphragmatic tissue from donor rats reseeded with allogenic bone marrow mesenchymal stromal cells. When transplanted, it regrew with the same complex mechanical properties of diaphragm muscle, functioning as well as undamaged organs.
“So far, attempts to grow and transplant such new tissues have been conducted in the relatively simple organs of the bladder, windpipe and esophagus. The diaphragm, with its need for constant muscle contraction and relaxation puts complex demands on any 3D scaffold; until now, no one knew whether it would be possible to engineer,” stated Taylor.
Macchiarini further explained: “This bioengineered muscle tissue is a truly exciting step in our journey towards regenerating whole and complex organs. You can see the muscle contracting and doing its job as well as any naturally-grown tissue – there can be no argument that these replacements are truly regenerated, and the possibilities that this opens up for the future are enormous.”
The next steps include testing the engineered tissue in larger animals then if successful in humans. It is hoped that that the engineered tissue could be used for congenital diaphragm defects and possibly future repairs of the heart. The treatment would hopefully be at least as effective as the existing surgical options but have the advantage of growing with children throughout their lives.
Sources: www.alphagalileo.org/ViewItem.aspx?ItemId=158969&CultureCode=en; Gubareva EA, Sjöqvist S, Gilevich IV et al. Orthotopic transplantation of a tissue engineered diaphragm in rats. Biomaterials doi:10.1016/j.biomaterials.2015.11.020 (2015).