Tailoring Stem Cells To Fashion Replacement Organs

In Biologics, Biotech Basics, Clinical Trials, Cocktail Fodder, FDA, Medical Device, The WEEKLY by Emily Burke

If stem cells have their way, replacement organs may find their place as a plentiful standard of treatment. This pairing prompted us to wonder: what is it about stem cells that make them attractive to organ replacement therapies?

The therapeutic potential of stem cells lies in their ability to differentiate into any cell type in the adult human body, depending on the type of stem cell. However, a potential disadvantage of tissues or organs derived from stem cells is rejection by the recipient’s immune system. A type of stem cell called an induced pluripotent stem cell has the potential to turn down the need for the immunosuppressive therapy that goes hand in hand with organ and tissue transplants.

With these new methodologies premiering on the runway, let’s take a look at stem cells as they set trends in tissue transplantation and organ replacement.

STEM CELL PRIMER

The challenge for scientists working in the stem cell lab is figuring out the exact cocktail of growth factors, hormones, and nutrients required to lead a stem cell down the correct and intended developmental path. To become a pancreatic cell, instead of a heart cell or a liver cell would be an example. Once the combination is perfected, scientists can differentiate cell types into their choosing. The ultimate goal is to use these new cells to produce replacement tissue and organs for patients suffering from degenerative diseases or traumatic injuries.

Embryonic stem cells are prized because of their potential to develop into any tissue in an adult human—a characteristic called pluripotency. By reactivating four genes that have been turned off during the progression from embryonic stem cell to specific tissue type, researchers can turn back the hands of time and create induced pluripotent stem cells (IPSC). The IPSC advantage is that there is less chance of rejection by a patient’s body.

To date, the only stem cell-based therapy approved by the FDA is New York Blood Center’s Hemacord, a cord blood product indicated for disorders related to the production of blood in the body. Clinical trials are ongoing for stem cell-derived therapies for diabetes, stroke, ALS, and spinal cord injury.

MIRACLE MESH WITH A SIDE OF STEM CELL

The Artificial Pancreas Project, spearheaded by JDRF, aimed to fund the development of new technologies in diabetes. The goal was to replace the diabetic’s damaged pancreas and reduce or even eliminate the need for constant self-monitoring of blood glucose and insulin levels. The most exciting outcome after a decade of labor? Viacyte’s (San Diego, CA) artificial pancreas derived from embryonic stem cells, which gained approval to enter clinical trials earlier this month.

Viacyte’s true innovation comes from their planned delivery of these cells: encapsulation in a biocompatible mesh. This miracle mesh simultaneously shields the cells from the patient’s immune system, yet still allows oxygen and nutrients to enter, supporting the cells’ growth and maintenance. Most importantly, insulin and other hormones secreted by the pancreas are able to exit the device, potentially doing away with the need for insulin injections.

What other organs are being derived from a combination of stem cells and device?

Over the past few years, a handful of patients with damaged tracheas have received synthetic versions attained from stem cells layered onto a fabricated scaffold engineered by Harvard Apparatus Regenerative Technology (Holliston, MA).

Tengion (Winston-Salem, NC) is currently conducting clinical trials using muscle stem cells overlaid on a scaffold system to grow custom urinary conduit systems, used in patients who have cancerous bladders removed.

Other structurally simple organs ideally suited for scaffolding technology include esophagus, bladder, and heart valves.

COCKTAIL FODDER

  • The only place one may buy an organ legally is in the country of Iran; however, citizenship is required in order to lessen transplant tourism.
  • Australia is entertaining the idea of legal monetary compensation for organs.
  • Singapore has yet to actually execute the process of paying donors but has legalized a compensation plan.

BIOINKED: THE NEW REALITY SHOW

Bioprinting is another approach for tissue production. Bioink, a mixture of cells (including stem cells) and hydrogel can be layered into three-dimensional shapes using modified 3D printers.

The first company to whip up a working bioprinter is Organovo (San Diego, CA) with NovoGen MMX Bioprinter. Since bioprinting its first blood vessel in 2010, Organovo has jumped to presenting bioprinted liver tissue for drug discovery earlier this year.

The bioprinting of skin (the largest organ in the human body) onto burn wounds is being tested in clinical trials sponsored by Wake Forest School of Medicine and the Armed Forces Institute of Regenerative Medicine (Ft. Detrick, MD).

At this time, complex organs cannot be produced due to limitations in bioprinting and the challenge of creating a robust vascular system.