In a ground-breaking development, scientists at Harvard University and the Broad Institute of MIT and Harvard have successfully produced the first-ever 3D brain models, or "chimeroids," using cells taken from numerous individuals. Compared to earlier models, these hybrid creations, a kind of brain organoids, more closely resemble the composition and capabilities of an actual human brain.

Paola Arlotta, a co-senior author of the research paper and a professor of stem cell and regenerative biology at Harvard University, led the study. Using growth-inducing chemicals, the researchers cultured individual brain organoids from the stem cells of five different donors. The cells from these organoids were subsequently reassembled to create the hybrid.

Brain organoids are usually cultivated from the cells of a single donor, which restricts their capacity to represent the genetic variation across individuals and its influence on brain development and pharmacological responses. Nevertheless, this restriction is removed by the new chimeroids, which have an equal amount of cells from five distinct individuals.

The University of California, Los Angeles (UCLA) associate professor Aparna Bhaduri, who was not involved in the study, stated, "Chimeroids are an exciting tool that will be widely adopted in the field of neurodevelopment, probably with diverse applications,"

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Image Source: UCLA

Chimeroids in Predicting Patient Responses

The chimeroids were made by taking stem cells from five different individuals and inducing them to grow into brain organoids, each of which contained cells from a single donor, using growth-inducing chemicals. After that, they disassembled the resulting organoids and mixed the cells again to create chimeroids.

Three months later, the 0.12 to 0.2-inch-diameter chimeroids exhibited all the cell types present in the fetus's brain.

"I'm excited about what the future holds in terms of using organoids, such as the chimeroids, to develop brand new ways to achieve therapeutic innovation for neurological disease," said Paola Arlotta, co-senior study author and a professor at Harvard University.

Chimeroids have the potential to assist in predicting patients' responses to medications before clinical trials by enabling the division of patients into distinct treatment response groups if they are expanded to incorporate cells from more individuals.

Unlike animal models that are developed from a single genetic background, the genetic variability reflected more closely matches the variation observed in human populations. The chimeroids' cells from various donors reacted differently to neurotoxic substances like ethanol and valproic acid in terms of growth impediment. This enables scientists to have a deeper understanding of how medications may affect individuals differently depending on their genetic composition.

Before going through clinical trials, chimeroids may be able to predict how each patient will react to medications; this would allow for more individualized treatment plans. This is a significant benefit over conventional animal models, which are unable to precisely forecast the unique medication responses of humans.

Advantages of Chimeroids Over Traditional Models

Chimeroids can replicate the structure and functions of a full-sized brain and contain all the cell types seen in the human cortex, in contrast to 2D cell cultures or animal models. Compared to more straightforward in vitro systems or animals like mice and rats, this makes them a more physiologically appropriate model for researching brain development and testing neurological medications.

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