by All mammals that produce milk have mammary glands, a feature that has interested scientists for many years. Questions such as why mammalian glands evolved in the first place, how they changed across different species and what unique evolutionary pressures shaped their development remain largely unanswered.
To investigate how different species have developed unique solutions to biological challenges, my team at the Rauner Lab of Tufts University School of Medicine is recreating mammalian diversity in a dish through miniature versions of mammalian glands – organisms. These models can shed light on the basic biological processes behind milk production, tissue regeneration and the early stages of breast cancer development.
What are organisms?
Organisms grown in a cell culture dish are 3D miniature structures that mimic the structure and function of real organs. These models are made by directing stem cells, which have the unique ability to differentiate into different types of cells, to form specific types of organ cells.
Although not exact replicas of full-sized organs, organisms contain enough cells and tissue architecture to recreate the environment and key functions of the organ they model. For example, mammary gland organoids or breast tissue organoids are composed of tiny elongated ducts that end in a spherical structure, mimicking the milk ducts and alveoli of the glandular tissue.
Organisms provide a powerful tool for biomedical research because they provide a 3D representation of organ structure and function. Unlike traditional 2D cell cultures, organisms can mimic the complexity of actual tissues, including their architecture and different cell types. This enables researchers to study complex biological processes such as tissue development, regeneration and disease progression, in a controlled environment, while reducing reliance on animal models.
A variety of mammals in a dish
Researchers have traditionally used organisms to model human diseases, test drugs and study developmental biology. However, their potential extends far beyond these applications, especially in the field of evolutionary biology.
My research focuses on generating mammary gland organisms from a variety of mammalian species. Mammals are extremely diverse, with each species adapted to a wide range of environments and lifestyles. The mammary gland, which is essential for the maintenance of offspring, shows considerable variation across species.
For example, monotremes such as the platypus and the echidna belong to a unique and ancient class of mammals. Monotremes diverged from other groups of mammals about 190 million years ago and are distinguished by their means of reproduction: laying eggs instead of live birth. Their mammary glands are very different from those of oestrous mammals such as cows and humans that have nipples; instead monotremes secrete milk through specialized maternal hairs.
Scientists believe that different environmental pressures and reproductive strategies promoted the evolution of different forms of lactation. However, the exact mechanisms and evolutionary pathways remain largely unknown. By comparing organisms from these diverse species, researchers can provide insight into how these ancient structures have evolved and adapted over millions of years to meet the reproductive needs of different animals.
Insights beyond the mammary gland
Studying the unique properties of mammary glands may shed light on other areas of biology and medicine.
For example, the mammary gland is able to regenerate with each cycle of reproduction and lactation. It is therefore an excellent model for studying tissue regeneration. With organoids, researchers can observe the regeneration process in real time and investigate how different species have evolved to maintain this regenerative ability. Understanding the mechanisms behind regeneration, a field that focuses on repairing or replacing damaged tissues and organs in conditions such as heart disease, diabetes and injuries, could lead to advances in regenerative medicine.
Mammary organisms may also contribute to breast cancer research. Studying mammalian organisms from species that rarely develop breast tumors, such as cows and pigs, could uncover potential protective mechanisms and inform new strategies to prevent and treat breast cancer in humans. Organisms also provide a platform to study the early events of tumor formation and the cellular environment that contributes to cancer development.
Organisms also enable scientists to study the initiation, duration and cessation of lactation in different species. The lactation process varies widely among mammals, influenced by factors such as hormonal changes and environmental conditions. Some mammals have unique forms of lactation. For example, marsupials such as the Tammar wallaby can produce two types of milk at the same time to meet the nutritional needs of the offspring at different developmental stages, a phenomenon known as simultaneous asynchronous lactation. In addition, the fur seal can maintain lactation despite long periods without nursing.
Studying different types of lactation through mammalian organisms can provide deeper insights into how lactation is regulated, revealing evolutionary adaptations that may elucidate the biology of human lactation and improve livestock milk production strategies in the agriculture.
The potential of organic technology
Organisms offer several advantages over traditional animal models. For one, they provide a controlled environment for studying complex biological processes and enable scientists to perform multiple tests simultaneously, increasing research efficiency.
They also reduce the ethical concerns associated with animal research. Organisms can be generated from animals that are not available for live research, such as rare or endangered species.
In addition, organisms can be genetically modified to investigate specific genes and pathways, providing deeper insights into the molecular mechanisms underlying mammary gland biology.
Although organisms are a powerful tool, they are not without limitations. They cannot fully replicate the complexity of living tissues, and results from organ studies must be validated in living subjects. Despite these obstacles, advances in biotechnology continue to push the boundaries of what is possible, providing new opportunities to explore mammalian diversity and evolution.
By recreating the diversity of mammalian tissue in a dish, researchers can gain important insights into how different species have evolved to solve biological challenges, which could benefit human health, agriculture and science nourished.
This article is republished from The Conversation, a non-profit, independent news organization that brings you reliable facts and analysis to help you make sense of our complex world. It was written by Gat Rauner, Tufts University
Read more:
Gat Rauner received funding from the Department of Defense Breast Cancer Research Program
