A revival of parabiosis in biomedical research

Abstract

Modern medicine wields the power to treat large numbers of diseases and injuries most of us would have died from just a hundred years ago, yet many of the most devastating diseases of our time are still untreatable. Chronic conditions of age such as cardiovascular disease, diabetes, osteoarthritis or Alzheimer's disease turn out to be of a complexity that may require transformative ideas and paradigms to understand and treat them. Parabiosis, which is characterised by a shared blood supply between two surgically connected animals, may just provide such a transformative experimental paradigm. Although forgotten and shunned now in many countries, it has contributed to major breakthroughs in tumour biology, endocrinology and transplantation research in the past century. Interestingly, recent studies from the United States and Britain are reporting stunning advances in stem cell biology and tissue regeneration using parabiosis between young and old mice, indicating a possible revival of this paradigm. We review here briefly the history of parabiosis and discuss its utility to study physiological and pathophysiological processes. We argue that parabiosis is a technique that should enjoy wider acceptance and application, and that policies should be revisited to allow its use in biomedical research.

Figure 1. Parabiosis history and modern use

(a) The annual number of publications using parabiosis is shown from 1860–2013. Several studies are highlighted as they provided groundbreaking findings. (b) Publications including parabiosis experiments are listed for different countries. All values have been extracted from http://www.gopubmed.org

Figure 2. Circulatory system in parabiosis

Organism A and B share a common blood supply, which spontaneously develops through anastomosis post-surgery. Organisms with different physiologic conditions may be used for parabiosis in order to assess the systemic effect of one organism on a particular tissue of interest in its attached partner.

Figure 3. Heterochronic parabiosis

Using heterochronic pairings of young (A) and old (B) mice allows assessment of the effect of a young systemic environment on a particular local tissue of interest in the aged partner and vice versa. Isochronic pairings (AA or BB) are important controls to exclude surgery-related observations and to determine age-related changes in the systemic environment. Briefly, systemic body fluids such as blood, lymph or CSF are collected, assessed with OMICS tools such as protein, lipid or hormone arrays and analyzed for differential levels of soluble factors pre- and post-parabiosis. A particular tissue of interest is isolated, phenotypically characterized by flow cytometry, immunohistochemistry or epi-/genetic measures and analyzed for parabiosis-induced phenotypic changes. The integration of these data leads to the identification of individual candidate factors or cells that can subsequently be tested in a suitable mouse model.