Bone marrow on a chip
The latest development of Harvard University researchers in the field of creating "organs on a chip" reproduces the structure, functions and cellular composition of the bone marrow. The device, dubbed "bone marrow on a chip," will allow scientists to study the effects of drugs, toxic compounds and radioactive radiation on bone marrow without using animals.
The head of the study, Professor Donald E. Ingber, is leading a project aimed at creating so–called "organs on a chip" - small microfluidic devices that reproduce the physiology of organs of living animals. To date, researchers have already managed to create chips that reproduce key aspects of the functioning of the human lungs, heart, kidneys and intestines. Several more organ models are at different stages of development. The aim of the work on this technology is to replace the testing of new medicines and toxins contained in the environment on animals, as well as to develop a new approach to modeling human diseases.
Until now, to create organs on a chip, researchers have combined various types of cells forming the organ of interest to them on the surface of a microfluidic chip and provided a continuous supply of nutrients, excretion of decay products and mechanical action to which the corresponding tissues are exposed in the conditions of the body. However, the structure and functions of the bone marrow are so complex that its reproduction required the use of a fundamentally new approach.
The main difficulty is due to the existence of a close relationship between the bone marrow and bone tissue. The bone marrow is contained inside the spongy bones. Inside the bones of this type have a porous structure resembling the cells of a honeycomb. Different zones of this structure differ in temperature and oxygen saturation, while each of the numerous types of cells inhabiting the bone marrow prefers special conditions. Moreover, bone marrow cells interact with each other through the secretion and recognition of many biologically active molecules, which are a kind of signals that control their fate. Depending on the nature of these signals, hematopoietic stem cells and progenitor cells divide, differentiate, mature or self-destruct, and mature blood cells enter the bloodstream.
Instead of trying to reproduce this complex structure with the help of chips, the authors decided to use the "help" of mice. They placed dry bone powder inside an open ring shape the size of a coin-operated battery and implanted it under the skin on the animal's back.
After 8 weeks, a form was surgically removed from under the skin of the animal, inside which a bone fragment was formed, the analysis of which with the help of a specialized computer scanner demonstrated an internal structure similar to the structure of the viscera of the spongy bone.
A microscopic image of a bioengineered bone with a hole opening the spongy structure,
on which colored images of blood cells and vascular systems are superimposed,
filling the space between the bone plates.
Histochemical analysis of the cells inhabiting the formed spongy bone, as well as their sorting into fractions and evaluation of the cellularity of each fraction confirmed the identity of the formed tissue and bone marrow contained in the mouse femurs.
To maintain the functioning of the bioengineered bone marrow outside the animal's body, the researchers placed a surgically removed bone fragment on the surface of a microfluidic chip, ensuring its continuous supply of nutrients and excretion of decay products. This made it possible to maintain the full functioning of the bone marrow model for a week. The authors believe that this period is sufficient for testing the toxicity and effectiveness of experimental drugs.
"Bone marrow on a chip" has already passed the initial test for suitability for testing drugs. Just like the bone marrow of a live mouse, bioengineered bone marrow is subject to the destructive effects of ionizing radiation. However, a drug approved by the US Food and Drug Administration that protects the bone marrow of patients undergoing radiotherapy prevents the death of the "bone marrow on a chip" model.
The developers hope that in the future they will be able to grow a model of human bone marrow in the body of immunodeficient mice. This will make it possible to create easy-to-use models for screening drugs in order to select optimized individual therapy for patients. Also, "bone marrow on a chip" can be used to preserve the bone marrow of cancer patients undergoing courses of radio and chemotherapy highly toxic to the hematopoiesis system.
Another possible application of the new development is its use as a source of blood cells circulating in the artificial circulatory system, which ensures the functioning of the system of other "organs on a chip". Researchers have already received funding for a project aimed at creating a system of 10 "organs on a chip" to study complex physiological processes outside the human body.
Article by Yu-suke Torisawa et al. Bone marrow–on–a–chip replicates hematopoietic niche physiology in vitro published in the journal Nature Methods.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the Wyss Institute for Biologically Inspired Engineering:
Bone marrow-on-a-chip unveiled.
08.005.2014