Fight Aging!

Decellularization of donor organs and tissue sections has been demonstrated in laboratory animals and trialed in humans for some years now. It is clearly an improvement over straight organ donation in that it greatly reduces transplant rejection, and may even put a dent in the issue of organ availability by allowing the xenotransplantation of pig organs repopulated with human cells.

Absent some bold, unexpected, and rapid advances in tissue engineering, I would expect that decellularization will become the mainstay technology for organ and tissue transplantation for the next two decades or so. The process of removing cells from tissue while leaving behind the extracellular matrix and its chemical guides is comparatively simple and it dovetails well with present progress in control over stem cells and cell growth, enabling emptied organs to be reliably repopulated with a patient's own cells and made to work once again. Further, it circumvents a very hard problem, which is to say the challenge of creating an artificial scaffold that works as well as a biological extracellular matrix for these purposes. That has only been effectively achieved for small amounts of comparatively simple tissues such as muscle, and even there the real thing is generally better. There is a way to go yet in tissue engineering before decellularization will cease to be an extremely useful technology.

These publicity materials note recent work on engineering replacement heart valves for children using decellularized tissues, something that was being done in Europe far back as six years ago. Research proceeds on an uneven front, and some groups are always years out in front of others. This is but one among many applications of decellularization that will follow in the years ahead, and the expertise and inclination to follow this path is spreading, albeit more slowly than we'd all like.

Skin Cells Can Be Engineered Into Pulmonary Valves for Pediatric Patients

Researchers have found a way to take a pediatric patient's skin cells, reprogram the skin cells to function as heart valvular cells, and then use the cells as part of a tissue-engineered pulmonary valve. "Current valve replacements cannot grow with patients as they age, but the use of a patient-specific pulmonary valve would introduce a 'living' valvular construct that should grow with the patient. Our study is particularly important for pediatric patients who often require repeated operations for pulmonary valve replacements." While the study was conducted in vitro (outside of the body), the next step will be implanting the new valves into patients to test their durability and longevity.

Engineering Patient-Specific Valves Using Stem Cells Generated From Skin Biopsy Specimens

We generated induced pluripotent stem cells (iPSCs) by reprogramming skin fibroblast cells. We then differentiated iPSCs to mesenchymal stem cells (iPCSs-MSCs) using culture conditions that favored an epithelial-to-mesenchymal transition. Next, decellularized human pulmonary heart valves were seeded with iPCS-MSCs using a combination of static and dynamic culture conditions and cultured up to 30 days. Our results demonstrate the feasibility of constructing a biologically active human pulmonary valve using a sustainable and proliferative cell source. The bioactive pulmonary valve is expected to have advantages over existing valvular replacements, which will require further validation.

Ultimately even very sophisticated transplants are a stepping stone technology: no-one really wants to be opened up for surgery if there are better alternatives. The better alternative will probably emerge naturally as control over cells continues to evolve. Don't build the ship outside the bottle if you can build it inside the bottle. Find ways to control the necessary regrowth and regeneration of damaged organs in situ by making the cells already present in the body perform the needed actions in concert. That lies a way beyond decellularization as a practical and going concern, widespread in hospitals and clinics, but not a very long way beyond.