Harnessing pluripotent stem cells as seeds for growing new organs.

Summary

Dr. Anthony Atala describes regenerative medicine as the use of cells and engineered tissues to repair or replace body structures. His laboratory at the Wake Forest Institute for Regenerative Medicine works on about 40 tissue and organ types. Atala says roughly 18 technologies have been transferred to patients.

He groups engineered structures by increasing architectural complexity:

• Flat tissues, such as skin, which still contain multiple cell types and layers.
• Tubular structures, such as blood vessels and the urethra.
• Hollow organs, such as the bladder, uterus, and stomach.
• Solid organs, such as the heart, liver, lungs, and kidneys.

Atala says his group has developed approaches across all four categories. The bladder was the group’s first permanent organ replacement in a human. Other examples he mentions include work involving blood vessels, cartilage, skeletal muscle, and kidney tissue.

How engineered tissues are developed

The process involves:

1. Identifying and growing the relevant cells while ensuring they retain their normal characteristics and function.
2. Choosing or developing suitable biomaterials and scaffolds for the cells.
3. Combining cells and materials into a three-dimensional structure.
4. Testing the construct in living models and assessing whether it functions.
5. Using 3D printing to improve the scalability and reproducibility of a process already worked out in cell biology and materials science. The printer does not simply produce a ready-to-use organ.

Atala emphasizes that each tissue requires its own research and that developing a therapy for patients can take a decade or more—sometimes two decades. He says his group has generally waited until patients in an engineered-tissue study had at least five years of follow-up before publishing results.

Scaffolds, donor organs, and cells

Atala describes two broad strategies:

• Build a structure using cells and biomaterials.
• Take a discarded donor organ, wash away its cells with mild detergents, and repopulate its remaining scaffold with the patient’s cells.

He says the scaffold itself does not trigger the same rejection concern as donor cells, while using a patient’s own cells can help avoid cell-mediated rejection.

His group generally prefers patient-specific cells, although obtaining and expanding them can be difficult. For patients whose own cells are unavailable or unsuitable, donor stem cells may be an alternative, but immune compatibility—including HLA—remains an issue.

Stem cells and future transplantation

Atala distinguishes adult stem cells, which he describes as limited to particular cell lineages, from embryonic stem cells and induced pluripotent stem cells, which can give rise to cells from all three germ layers. He notes a major challenge with pluripotent cells: their tendency to form tumors.

He also describes a placental stem-cell population that, according to him, can produce cells from all three germ layers and is available at birth. He proposes banking these cells as a potential source for a broadly useful, HLA-matched donor pool. He estimates that a bank of about 100,000 specimens could provide a close genetic match for more than 80% of the U.S. population.

Atala stresses that regenerative medicine is not likely to remove the need for HLA expertise or transplantation services soon. He cautions against media coverage that makes experimental results sound immediately available to patients: promising animal studies or an early human case do not establish that a treatment is safe, effective, or ready for widespread use.

Researchers and sources featured

• Dr. Anthony Atala — Director of the Wake Forest Institute for Regenerative Medicine and the featured scientific guest.
• National Institutes of Health (NIH) — Cited by Atala in discussing the definition of pluripotency and tumor formation.
• Wake Forest Institute for Regenerative Medicine — Atala’s research institute.

No specific research papers or additional researchers are named in the interview.