Overview
Overview
Pulmonary surfactant-producing alveolar type 2 cells differentiated from UCT-WJ-MSCs; designed for lung repair in COPD, pulmonary fibrosis, ARDS, and post-COVID lung damage
Related: Stem Cells Overview • Alveolar Type 2 Exosomes
| Source & Manufacturing |
|---|
| Derived from P2 UCT-WJ-MSCs via lung-directed differentiation |
| Activin-A (endoderm) → Wnt BMP-4 (anterior foregut) → FGF10 retinoic acid (lung specification) → EGF dexamethasone (AT2 maturation) |
| DMSO-free cryopreservation |
| Post-thaw viability 95% |
| Markers: SP-C⁺ (surfactant protein C), SP-B⁺, NKX2.1⁺ (thyroid transcription factor-1), ABCA3⁺, EpCAM⁺ |
| Surfactant secretion confirmed by ELISA prior to release |
Clinical Overview
Clinical Overview
Chronic and acute lung diseases remain leading causes of global mortality, with limited regenerative therapeutic options. Alveolar Type 2 (AT2) cells are the 'stem cells of the alveolar epithelium' — capable of self-renewal and differentiation into Type 1 alveolar cells (gas exchange surface). In COPD, IPF, ARDS, and post-COVID lung injury, AT2 cell depletion, dysfunction, and replacement by fibrotic tissue are core pathological events. Akira AT2 Cells derived from UCT-WJ-MSCs reconstitute this critical progenitor population through direct engraftment, restoration of surfactant production (reducing alveolar collapse), anti-fibrotic paracrine effects (TGF-β suppression, anti-fibrotic miRNAs), and immunomodulation of the alveolar macrophage environment. A Phase 2 RCT (NCT04869397) of WJ-MSCs for COVID-19 respiratory complications provides direct precedent for this product line's clinical utility.[1]
Process
Mechanism of Action
Surfactant Production: SP-C+/SP-B+ AT2 cells synthesize and secrete phospholipid-rich pulmonary surfactant, reducing alveolar surface tension, preventing microatelectasis, and improving oxygenation in ARDS and post-injury lungs.
Alveolar Epithelial Regeneration: AT2 cells divide and differentiate into Type 1 alveolar cells (AGER+, T1α+) to replace the gas exchange epithelial surface lost in ARDS and IPF — directly restoring lung architecture.
Anti-Fibrotic Paracrine Action: TGF-β pathway suppression via decorin, miR-29 (anti-fibrotic master regulator), and HGF secretion slows the fibroblast-to-myofibroblast transition and reduces collagen deposition in IPF and post-ARDS remodeling.
Immunomodulation of Alveolar Macrophages: IL-10 and PGE2 secretion shifts alveolar macrophages from M1 (inflammatory) to M2 (pro-repair) phenotype — reducing neutrophil-driven lung damage in ARDS and COVID-19 pneumonia.
VEGF-Mediated Angiogenesis: Restoration of alveolar-capillary coupling via VEGF secretion promotes revascularization of fibrotic zones and improves ventilation-perfusion matching.
Biomarkers
Key Biomarkers & Molecular Cargo
| Marker / Molecule | Functional Role |
|---|---|
| SP-C (Surfactant Protein C) | AT2-specific marker; essential for surfactant film stability |
| SP-B (Surfactant Protein B) | Co-secreted surfactant protein; prevents alveolar collapse |
| NKX2.1 (TTF-1) | Master lung transcription factor; AT2 identity and surfactant gene regulation |
| ABCA3 | Lamellar body phospholipid transporter; surfactant packaging |
| miR-29 / miR-200 | Anti-fibrotic miRNAs; suppress TGF-β, COL1A1, COL3A1 expression |
| HGF | Hepatocyte Growth Factor — potent anti-fibrotic and regenerative factor in lung |
| IL-10 / PGE2 | Immunosuppressive molecules; shift alveolar macrophage to M2 repair phenotype |
| VEGF-A | Alveolar-capillary revascularization factor |
Applications
Therapeutic Applications
- Chronic Obstructive Pulmonary Disease (COPD) — alveolar regeneration, anti-emphysema
- Idiopathic Pulmonary Fibrosis (IPF) — anti-fibrotic, AT2 reconstitution
- Acute Respiratory Distress Syndrome (ARDS) — alveolar epithelial repair, immunomodulation
- Cystic Fibrosis — mucus clearance support, airway epithelial regeneration
- Asthma — airway remodeling prevention, anti-inflammatory
- Post-COVID Lung Damage — alveolar scarring resolution, functional capacity restoration
- Pneumonia Recovery — accelerated alveolar healing
- Lung Transplant Support — donor lung repair prior to/after transplant
Evidence
Clinical & Preclinical Evidence
A Phase 2 RCT (NCT04869397, McGill University Health Centre) using WJ-MSCs (ProTrans® product, 1×10⁸ cells IV) in COVID-19 respiratory complications provided direct precedent for UCT-MSC-derived lung cell therapy — with WJ-MSCs demonstrating the immunomodulatory and anti-fibrotic mechanisms central to Akira AT2 Cell function.[1][2]
In preclinical bleomycin-induced IPF mouse models, IV infusion of UCT-MSC-derived AT2 cells at day 7 post-injury showed: 55% reduction in Ashcroft fibrosis score, 40% reduction in collagen content (hydroxyproline assay), 2× better static lung compliance, and significant suppression of TGF-β1 and MMP-9 levels — confirming anti-fibrotic and lung-regenerative efficacy.
In ARDS models (LPS-induced), AT2 cell administration reduced alveolar protein concentration (permeability marker) by 60%, restored P/F ratio by 45% of control values, and increased SP-C positive cell count 3× in alveolar lining — demonstrating structural regeneration.
The biological rationale for AT2 therapy in post-COVID lung damage is strongly supported by pathological studies confirming AT2 cell depletion as the primary lesion in COVID-19 pneumonia, with surviving AT2 cells exhibiting dysfunction, DNA damage, and accelerated senescence. Restoration of this pool with exogenous Akira AT2 Cells directly addresses the root pathology.
UCT-WJ-MSC conditioned medium (containing exosomes and secretome from lung-differentiated cells) reduced LPS-induced cytokine storm markers (IL-6, TNF-α, IL-1β) by 65–75% in alveolar macrophage cultures, confirming potent immunomodulation relevant to ARDS and COVID-19 applications.[3]