Lung ischemia-reperfusion (IR) injury is a serious complication, particularly after lung transplantation, often leading to primary graft failure and long-term impaired lung function. While stem cell therapies hold great promise, not all stem cells are created equal. A groundbreaking study published in Cell Transplantation investigates the potential of a unique stem cell type – Human Multilineage-differentiating Stress-Enduring (Muse) cells – and their superior ability to heal acute lung IR injury compared to traditional mesenchymal stem cells (MSCs).
The Challenge of Lung IR Injury
When a lung is deprived of blood flow (ischemia) and then reperfused (blood flow restored), it can suffer significant damage. This “ischemia-reperfusion injury” is a major hurdle in lung transplantation, affecting both patient survival and the function of the transplanted organ. Researchers have long explored stem cells, like MSCs, for their regenerative properties. However, as the study notes, MSCs sometimes “failed to yield statistically meaningful efficacy in patients with acute respiratory distress syndrome,” partly because “only a few cells remain in the target organ and therefore remain in damaged tissues for short periods of time.” (p. 1)
Enter Muse Cells: A Novel Approach to Regeneration
Muse cells are a fascinating type of endogenous reparative stem cell. They are “nontumorigenic,” meaning they don’t form tumors, and are “easily harvested” from various tissues. What makes them particularly exciting is their “stress-tolerant” nature and “pluripotent-like” qualities, allowing them to differentiate into various cell types.
The study, led by Hiroshi Yabuki and colleagues, aimed to compare the therapeutic effects of human Muse cells against human MSCs in a rat model of acute lung IR injury.
Key Findings: Muse Cells Outperform MSCs
The results were compelling, demonstrating Muse cells’ remarkable efficacy:
- Improved Lung Function: Rats treated with Muse cells showed significantly better lung function. On day 5 post-treatment, the Muse group’s P/F ratio (a measure of oxygen efficiency) was approximately 1.7-fold higher than the MSC group and 3.2-fold higher than the vehicle group. They also exhibited improved left lung compliance, indicating better elasticity and function.
- Reduced Tissue Damage: Histological analysis revealed that Muse cells significantly reduced injury parameters like intra-alveolar edema, hemorrhage, capillary congestion, and neutrophil infiltration in the lung tissue. This suggests a powerful protective effect at the cellular level.
- Enhanced Homing and Survival: One of the critical advantages of Muse cells was their ability to home to the injured lung more efficiently. The researchers observed “approximately 12.5-fold higher” numbers of Muse cells in the injured lung compared to MSCs on day 3. This better engraftment is crucial for sustained therapeutic effect.
- Anti-Apoptotic and Pro-Proliferative Effects: Muse cells actively combated cell death (apoptosis) and stimulated the regeneration of host alveolar cells. The study found that Muse cells suppressed apoptosis by 39% and 46% compared to the vehicle and MSC groups, respectively, on day 3. They also boosted the proliferation of type II alveolar epithelial cells, which are vital for lung repair, by “approximately 3.5- and 3-fold higher than those in the vehicle and MSC groups.” (p. 7)
- Secretory Powerhouse: In laboratory tests, Muse cells proved to be superior producers of several beneficial substances compared to MSCs. These include:
- HGF (Hepatocyte Growth Factor): ~2.8-fold more
- Angiopoietin-1: ~1.4-fold more
- KGF (Keratinocyte Growth Factor): ~2.4-fold more
- PGE2 (Prostaglandin E2): ~5.4-fold more
- These factors play crucial roles in reducing inflammation, preventing apoptosis, improving vascular permeability, and stimulating tissue repair.
Why Muse Cells Are Different
The study highlights that Muse cells’ advantages stem from two core characteristics:
- Targeted Migration: Muse cells demonstrated a “stronger migratory capacity toward serum from IR injury model rats than did MSCs,” suggesting they can actively seek out and migrate to damaged tissues. (p. 8)
- Stress Tolerance: They “express factors related to stress tolerance and immunomodulation,” allowing them to survive and function effectively in the harsh, inflamed environment of an injured lung, where other cells might struggle. (p. 1)
The Road Ahead
While these findings are highly promising, the authors acknowledge that further research is needed, particularly in actual lung transplantation models and human trials. However, the study concludes that “Muse cells efficiently ameliorated lung IR injury via pleiotropic effects in a rat model. These findings support further investigation on the use of human Muse cells for lung IR injury.” (p. 1)
The potential for Muse cells to provide a more robust and effective cell therapy for lung IR injury is immense, offering a beacon of hope for patients undergoing lung transplantation and other acute lung conditions.
References:
Yabuki, H., Wakao, S., Kushida, Y., Dezawa, M., & Okada, Y. (2018). Human Multilineage-differentiating Stress-Enduring Cells Exert Pleiotropic Effects to Ameliorate Acute Lung Ischemia-Reperfusion Injury in a Rat Model. Cell Transplantation, 27(6), 979–993. https://pubmed.ncbi.nlm.nih.gov/29707971/