Academic Journal
MISSTE: a multiscale integrative spatial simulator for understanding the mechanisms underlying tissue ecosystems.
| Τίτλος: | MISSTE: a multiscale integrative spatial simulator for understanding the mechanisms underlying tissue ecosystems. |
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| Συγγραφείς: | Su Z; Research, Takeda Pharmaceutical Company Ltd., Cambridge, MA, 02139, USA., Yin S; Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA., Wu Y; Department of Systems and Computational Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA. Electronic address: yinghao.wu@einsteinmed.edu. |
| Πηγή: | Computers in biology and medicine [Comput Biol Med] 2026 Aug 15; Vol. 213, pp. 111838. Date of Electronic Publication: 2026 Jun 28. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: United States NLM ID: 1250250 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0534 (Electronic) Linking ISSN: 00104825 NLM ISO Abbreviation: Comput Biol Med Subsets: MEDLINE |
| Imprint Name(s): | Publication: New York : Elsevier Original Publication: New York, Pergamon Press. |
| Ιατρικοί όροι (MeSH): | Tumor Microenvironment*/immunology , Neoplasms*/immunology , Neoplasms*/therapy , Neoplasms*/pathology , Computer Simulation* , Models, Biological*, Humans ; Animals |
| Περίληψη: | Multiscale tissue ecosystems are governed by coupled intracellular decision-making, cell-cell interactions, and spatially structured microenvironmental signals, yet these scales are often studied separately. Here we present MISSTE, a modular framework that integrates Boolean intracellular state logic, agent-based modeling, and partial differential equation fields within a unified spatial simulation architecture. As a proof of concept, we applied MISSTE to CAR-T therapy in a solid tumor microenvironment. The model recapitulated emergent features of CAR-T behavior, including limited tumor penetration, stromal suppression, localized cytokine remodeling, hypoxia-associated constraint, and progressive functional exhaustion. Comparison of baseline and optimized conditions showed that coordinated enhancement of interaction range, migration, and cytotoxic function improved immune persistence and partial tumor control. Systematic parameter scans further identified effective immune-tumor contact as a stronger determinant of outcome than killing strength alone, highlighting spatial access as the dominant bottleneck. Guided by these results, we designed sequential intervention strategies and found that time-ordered enhancement of infiltration, killing, and late functional protection outperformed a static optimized regime. Together, these results establish MISSTE as a generalizable multiscale methodology for dissecting tissue ecosystems and for generating mechanistically grounded strategies for engineered cellular therapy design. (Copyright © 2026 Elsevier Ltd. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Σχόλια: | Update of: bioRxiv. 2026 Apr 16:2026.04.14.718434. doi: 10.64898/2026.04.14.718434.. (PMID: 42039431) |
| Entry Date(s): | Date Created: 20260628 Date Completed: 20260722 Latest Revision: 20260722 |
| Update Code: | 20260723 |
| DOI: | 10.1016/j.compbiomed.2026.111838 |
| PMID: | 42365718 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1879-0534 |
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| DOI: | 10.1016/j.compbiomed.2026.111838 |