생체 내 재생의료(IVRM) : 내인성 줄기세포 활성화, 조직 니치 재생 및 장기 수복 - 기술 상황, 임상 개발 파이프라인 및 세계 시장 전망(2025-2040년)

Executive Summary / Description

In-vivo regenerative medicine (IVRM) aims to repair tissues by activating the body's own regenerative circuits-mobilizing endogenous stem/progenitor cells, rejuvenating the extracellular matrix (ECM) and niches, re-establishing neuro-immune resolution, and restoring organ function without exogenous cell transplantation. It combines regeneration-inducing biologics, niche-targeted chemokines, ECM instructive materials, immune re-training, and increasingly gene/RNA interventions to program organ-specific repair.

Why now?

• Aging & chronic disease load (cardio-metabolic, pulmonary, hepatic, renal, musculoskeletal, neurodegeneration).
• Cell therapy bottlenecks (cost, logistics, durability, safety) -> demand for off-the-shelf in-vivo options.
• Mechanistic clarity in stem-cell niches, inflammation resolution, senescence, and ECM mechanics.
• Platform convergence: omics + spatial biology + AI tissue models + targeted delivery (LNPs, exosomes, peptide shuttles).

Technology Vectors Shaping IVRM

1. Endogenous stem/progenitor recruitment (SDF-1/CXCL12-CXCR4 axis; HGF, Wnt/RSPO; Notch tune).

2. Niche rejuvenation (mechanotransduction reset; matricellular proteins; glycosaminoglycan editing).

3. Senescence & SASP control (senolytics/senomorphics; epigenetic reprogramming pulses).

4. Immuno-regeneration (pro-resolving lipid mediators, macrophage re-education M1->M2, Treg induction).

5. Neuro-regeneration (axon guidance cues, Schwann/oligodendrocyte support, ECM laminins).

6. Bioactive scaffolds in situ (injectables, hydrogels, ECM-mimetics with drug/RNA depots).

7. In-vivo gene/RNA signals (saRNA/circRNA for growth factors; CRISPR/ADAR edits to unlock regenerative states).

8. Organotropic delivery (heart, liver, lung, kidney, skeletal muscle, cartilage, retina, CNS).

Commercial Outlook (2025-2040)

Market expansion from ~USD 2.5-3.5B (2024) experimental/early categories -> USD 25-35B by 2035 and USD 60B+ by 2040, driven by:

• Musculoskeletal (cartilage/meniscus, tendon, intervertebral disc).
• Cardiac micro-repair post-MI; heart failure remodeling.
• Liver fibrosis regression & NASH resolution.
• Diabetic wound healing & limb salvage.
• Pulmonary fibrosis micro-repair.
• Neuro-repair (peripheral nerve; early CNS segments).

Business models: procedure-adjacent biologics (ASC reimbursement), chronic maintenance dosing (q3-6 months for fibrosis regression), combination packs (drug + hydrogel), and platform licensing to device companies and hospital systems.

In-Vivo Regeneration - Technology Understanding

Core Mechanisms (first principles)

• Recruit: Mobilize endogenous repair cells (BM-MSC, tissue-resident progenitors, satellite cells) via chemokines (e.g., CXCL12/SDF-1, CCL2, HGF, PDGF, VEGF), and mechanical cues (YAP/TAZ).
• Rejuvenate: Normalize niche stiffness and ECM composition (collagen crosslinking, laminin isoforms, fibronectin splice variants), down-modulate TGF-B fibrogenic loops.
• Resolve: Switch inflammation -> resolution (SPMs: resolvins, protectins, maresins); educate macrophages; expand Tregs.
• Replace/Remodel: Drive angiogenesis, axon sprouting/remyelination, cardiomyocyte/satellite cell cycling, hepatocyte proliferation.
• Reset: Short pulses of partial epigenetic reprogramming (e.g., OSK-like transcriptional programs) to restore youthful gene expression without loss of identity (tight control circuits).

Modality Archetypes

• Regeneration-inducing biologics (recombinant growth factors; engineered cytokines; pro-resolving mediators).
• Chemokine mimetics & GPCR agonists (CXCR4 agonist/antagonist timing logic).
• RNA gene-expression infusions (saRNA/circRNA for HGF/VEGF/IGF-1; micro-dosed tissue-specific factors).
• Small-molecule niche modulators (FAK, LOX, integrin, ROCK, TGF-B/ALK5, Wnt/Notch modulators).
• Senescence therapeutics (senolytics: BCL-2 family; senomorphics: JAK/STAT, mTOR tuning).
• Bioactive hydrogels & ECM mimetics (in situ forming, shear-thinning, adhesive peptides, MMP-responsive).
• Targeted delivery (LNPs with organotropic lipids; peptide shuttles; exosome carriers; micro-needle arrays).

Table of Content

1. Introduction & Methodology

• 1.1 Scope, definitions (in-vivo vs ex-vivo regeneration)
• 1.2 Evidence grading, KOL methodology, trial sources
• 1.3 Technology readiness levels (TRL) for IVRM

2. Biology of Regeneration & Tissue Niches

• 2.1 Stem/progenitor hierarchies by organ
• 2.2 ECM & mechanobiology of repair
• 2.3 Inflammation -> resolution continuum
• 2.4 Senescence & SASP in aging tissue microenvironments
• 2.5 Neural & vascular coupling in regeneration

3. Modality Landscape & Platform Technologies

• 3.1 Regeneration-inducing biologics
• 3.2 Chemokine-GPCR programming
• 3.3 Niche-rejuvenation & antifibrotics
• 3.4 Senolytics & senomorphics
• 3.5 RNA/Gene in-vivo programming
• 3.6 Bioactive scaffolds
• 3.7 Organ-targeted delivery tech

4. Organ-Specific Opportunity Maps

• 4.1 Cardiovascular: MI micro-repair, micro-angiogenesis, scar remodeling
• 4.2 Liver: NASH fibrosis regression, cholestatic injury repair
• 4.3 Lung: IPF micro-repair, alveolar regeneration
• 4.4 Kidney: AKI -> CKD prevention; tubular repair
• 4.5 Musculoskeletal: cartilage/meniscus, tendon, skeletal muscle satellite-cell activation
• 4.6 Dermatology & Wounds: diabetic ulcers, radiation injury, burns
• 4.7 Neurology: PNS repair (Schwann), spinal cord bridging (adjunct), early retinal/optic
• 4.8 Endocrine/Metabolic: pancreatic islet niche protection (adjunct to metabolic control)

5. Clinical Development Landscape

• 5.1 Pipeline census by organ, modality, and stage
• 5.2 Key Phase II/III programs and readouts
• 5.3 Trial design
• 5.4 Safety & tolerability

6. Market Access & Commercial Strategy

• 6.1 Pricing scenarios
• 6.2 Reimbursement routes
• 6.3 Provider adoption

7. Competitive & Deal Landscape

• 7.1 Licensing & co-dev trends
• 7.2 M&A outlook & strategic acquirers
• 7.3 Regional dynamics (US/EU vs Japan/Asia)

8. Forecasts & Scenarios (2025-2040)

• 8.1 Base/Bull/Bear uptake by organ system
• 8.2 Peak share vs standard of care (SoC) sensitivity
• 8.3 Risked NPV drivers (clinical success probabilities by class)

9. Strategic Outlook

• 9.1 Five-year milestones & catalysts

10. Appendix