Humanized chimeras for the prospective assessment of cell addition and replacement therapies
Inventors
Goldman, Steven A. • Vieira, Ricardo da Costa Barbedo
Assignees
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Publication Number
US-12648547-B2
Publication Date
2026-06-09
Expiration Date
Abstract
A chimeric non-human mammal disease model, wherein (1) at least 30% of all the glial cells in the corpus callosum of the chimeric non-human mammal are human glial cells, and/or (2) at least 5% of all of the glial cells in the white matter of the brain and/or brain stem of the chimeric non-human mammal are human glial cells, and wherein the human glial cells comprise a combination of a first group of human glial cells tagged with a first label and a second group of human glial cells tagged with a second label that is distinguishable from the first label.
Core Innovation
The invention concerns a method for producing a chimeric non-human mammal comprising human glial cells. The method introduces a first population of human glial progenitor cells into the brain and/or brain stem of the non-human mammal, where the first population is tagged with a first detectable label, and introduces a second population of human glial progenitor cells tagged with a second detectable label distinguishable from the first detectable label.
After the introducing steps, the method recovers the chimeric non-human mammal with human glial cells in which the first human glial cells are derived or differentiated from the first population and remain tagged with the first detectable label, and the second human glial cells are derived or differentiated from the second population and remain tagged with the second detectable label. The chimeric mammal is characterized by having at least 30% human glial cells in the corpus callosum and/or at least 5% human glial cells in the white matter of the brain and/or brain stem.
The method further includes a functional interaction in which at least some of the second human glial cells induce apoptosis of some of the first human glial cells. Dependent aspects further define the source relationship of the human glial progenitor populations as disease-specific versus healthy, and further characterize the chimeric mammal by specifying particular disease contexts for the human disease-specific glial cells.
Claims Coverage
The provided material includes one independent claim. This independent claim includes three main inventive aspects: dual, distinguishably labeled human glial progenitor introductions; quantitative human glial cell abundance in defined brain regions; and an induced functional interaction in which second-population glial cells induce apoptosis of first-population glial cells.
Dual population dual-label human glial progenitor introduction
A method producing a chimeric non-human mammal comprising human glial cells by introducing a first population of human glial progenitor cells tagged with a first detectable label and a second population of human glial progenitor cells tagged with a second detectable label distinguishable from the first detectable label into the brain and/or brain stem.
Recovered chimera with labeled, derived human glial cells
Recovering, as a result of said introducing, a chimeric non-human mammal with human glial cells comprising first human glial cells derived or differentiated from the first population and tagged with the first detectable label, and second human glial cells derived or differentiated from the second population and tagged with the second detectable label.
Human glial cell abundance in corpus callosum and/or white matter
Characterizing the recovered chimeric non-human mammal such that at least 30% of all the glial cells in the corpus callosum are human glial cells and/or at least 5% of all the glial cells in the white matter of the brain and/or brain stem are human glial cells.
Second population induces apoptosis of first population
At least some of the second human glial cells induce apoptosis of some of the first human glial cells.
The claim coverage centers on producing a chimera through two differently labeled human glial progenitor populations, obtaining labeled derived glial cells in defined brain regions at specified human glial abundance thresholds, and including a mechanism in which second-population glial cells induce apoptosis of first-population glial cells.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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