Stem cell therapy for inherited metabolic disorders of the liver

Abstract

Modern medicine has conquered an enormous spectrum of health concerns, from the neonatal to the geriatric, the chronically ill to the acutely injured. Among the unmet challenges remaining in modern medicine are inborn disorders of metabolism within the liver. Such inherited metabolic disorders (IMDs) often leave an otherwise healthy individual with a crippling imbalance. As the principal regulator of the body's many metabolic pathways, malencoded hepatic enzymes can drastically disrupt homeostasis throughout the entire body. Severe phenotypes are usually detected within the first few days of life, and treatments range from palliative lifestyle modifications to aggressive surgical procedures. While orthotopic liver transplantation is the single last resort "cure" for these conditions, research during the past few years has brought new therapeutic technologies ever closer to the clinic. Stem cells, therapeutic viral vectors, or a combination thereof, are projected to be the next, best, and final cure for IMDs, which is well-reflected by this generation's research initiatives.

Figure 1. Potential material for liver cell therapy

Transplantable cells for the correction of liver metabolic disorders may be considered from among several differentiation states. These cell populations may be considered analogous to well characterized stages of liver development. Accessibility, expandability and suitability for genetic manipulation must be considered when selecting cells for therapeutic strategies.

Figure 2. The curative approach to IMDs may evolve in many forms

Gene therapy could offer healthy copies of the corrupted gene directly to the patient via systemic infusion of a tissue-specific vector. Stem cell research is closing in on means to repopulate tissues from which a disease originates. For IMDs, transplantable stem cells will derive from a healthy allogenic donor, or from the patient, provided the cells are genetically corrected ex vivo.