Regenerative-system dysfunction in organ fibrosis: Maladaptive regeneration, fibrotic memory, and therapeutic reprogramming

Table 6 Relationship of the proposed framework to selected major reviews

Ref.	Principal scope	Overlap with this review	Additional emphasis of the present framework
Henderson et al[3], 2020	Fibrosis mechanisms and therapeutic development across organs	Immune-stromal interactions, ECM remodeling, and antifibrotic targets	Aligns repair-compartment identity with operational persistence tests and separates mechanism, memory, and clinical benefit
Zhu et al[4], 2021	Maladaptive regeneration and developmental pathways in NASH/fibrosis	Repair can become fibrogenic rather than simply insufficient	Compares seven organs without assuming identical progenitor biology; distinguishes persistent repair from directly tested memory
Distler et al[5], 2019	Shared and organ-specific fibrosis mechanisms	Conserved signaling alongside disease- and organ-specific biology	Uses model- and cell-specific directness to constrain cross-organ grades and therapeutic classification
Netea et al[67], 2020	Trained immunity in health and disease	Durable response changes and epigenetic/metabolic conditioning	Requires fibrosis-relevant endpoints and separates beneficial tolerance, ongoing niche stimulation, and autonomous retained states
Present review	Evidence-calibrated injury-repair-memory synthesis	Integrates established concepts rather than claiming a wholly new mechanism	Proposes testable links, explicit memory boundaries, a reprogramming/modulation/platform distinction, and a staged translational roadmap

This comparison describes differences in emphasis, not absence of related concepts from prior reviews or proof that the present framework is mechanistically superior. ECM: Extracellular matrix; NASH: Nonalcoholic steatohepatitis.