Rebuilding Bladders with Cell-Free Materials

Ying-jian Zhud and Mu-jun Luan from the Shanghai Jiao Tong University in Shanghai, China teamed up to examine a new way to regenerate the bladder.

Several different synthetic and natural biomaterials have been pretty widely used in tissue regeneration experiments, particularly in the regeneration of the urinary bladder. The vast majority of this work has been done in rat model systems, which are fairly good animals to model bladder pathology and regeneration.

To date, the attempted reconstructive procedures don’t seem to work all that well, and this is due to the lack of appropriate scaffolding upon which cells can attach, grow and spread to form the new bladder tissue. Any scaffolding material for the bladder has to provide a waterproof barrier and it has to be able to support several different cell types. While this might not sound difficult on paper, it is in fact rather difficult. Some biomaterials might be well tolerated by the body, but cannot be fashioned into the shape of the organ. Others might support the growth of cells quite well, but are not tolerated by the body.

Zhud and Luan addressed these issues by turning to two different compounds that would compose a two-layered structure. Such a two-layered structure would support the cell types of the bladder. The outside layer was composed of silk fibroin, which is very moldable and usually well tolerated by cells. The inner layer consisted of a natural, acellular matrix (or BAMG for bladder acellular matrix graft). They used this two-layered structure to regenerate an injured bladder in rats.

First of all, it was clear that this material was relatively easy to make and it also could be nicely molded and sewn into the existing bladder. Tissue stains showed something even more interesting: the bilayer scaffold promoted the growth and recruitment of smooth muscles, blood vessels, and even nerves in a time-dependent manner. So by 12 weeks after implantation, bladders reconstructed with the bilayered matrix displayed superior structural and functional properties without significant local tissue responses or systemic toxicity.

Thus, the silk/BAMG scaffold could potentially be a promising scaffold for bladder regeneration. It shows good tissue compatibility, and allows the growth of cells on it. More work is required to take this to the next step, and the scaffold will undoubtedly undergo some changes. But this work represents a terrific start to what might be a superior scaffold for bladder regeneration.

Multipotent Adult Progenitor Cells for Immunomodulation after Liver Transplantation

Mesenchymal stem cells and multipotent adult progenitor cells (MAPCs) have received a good deal of discussion by scientists as agent for solid organ transplant recipients. Why? Because these cells, with their ability to suppress unwanted immune responses might be able to reduce the need for drugs that suppress the immune system, which have extensive side effects.

The study under discussion today is the clinical course of the first patient of the phase I, dose-escalation safety and feasibility study, MiSOT-I (Mesenchymal Stem Cells in Solid Organ Transplantation Phase I).

The patient received a living-related liver graft, each patient was given one intraportal injection (injection into the portal vein) and one intravenous infusion of third-party MAPC in combination with a low-dose of an anti-tissue-rejection drug.

The results so far are still coming in, but it seems that the administration of the cells is easy and is technically feasible. How well did the patients tolerate them? Quite well it turns out. There was no evidence of acute toxicity associated with infusions of the MAPCs. Also, there was some indication that the patient’s white blood cells were less reactive to foreign substances. However, it is difficult to make definitive statements about the efficacy of this treatment at this time.

Recruitment and follow-up of participants in the MiSOT-I trial continue, and completion of the study is currently projected for autumn 2016.