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Establishing Human Lung Organoids and Proximal Differentiation to Generate Mature Airway Organoids
Published on: March 23, 2022
SARS-CoV-2 Infection and Lung Regeneration
Fuxiaonan Zhao1, Qingwen Ma1, Qing Yue1
1Department of Basic Medicine, Haihe Clinical School, Tianjin Medical University, Tianjin, China.
Abstract:
The lung is the primary site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced immunopathology whereby the virus enters the host cells by binding to angiotensin-converting enzyme 2 (ACE2). Sophisticated regeneration and repair programs exist in the lungs to replenish injured cell populations. However, known resident stem/progenitor cells have been demonstrated to express ACE2, raising a substantial concern regarding the long-term consequences of impaired lung regeneration after SARS-CoV-2 infection. Moreover, clinical treatments may also affect lung repair from antiviral drug candidates to mechanical ventilation. In this review, we highlight how SARS-CoV-2 disrupts a program that governs lung homeostasis. We also summarize the current efforts of targeted therapy and supportive treatments for COVID-19 patients. In addition, we discuss the pros and cons of cell therapy with mesenchymal stem cells or resident lung epithelial stem/progenitor cells in preventing post-acute sequelae of COVID-19. We propose that, in addition to symptomatic treatments being developed and applied in the clinic, targeting lung regeneration is also essential to restore lung homeostasis in COVID-19 patients.
Insights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disrupts lung regeneration by targeting stem cells expressing ACE2. Targeting lung repair is crucial for COVID-19 recovery and preventing long-term damage.
Area of Science:
- Pulmonary Medicine
- Immunopathology
- Regenerative Medicine
Background:
- The lung is the primary site of SARS-CoV-2-induced immunopathology, with the virus entering host cells via ACE2.
- Lung stem/progenitor cells express ACE2, posing a risk of impaired lung regeneration post-infection.
- Clinical treatments like mechanical ventilation may also impact lung repair mechanisms.
Purpose of the Study:
- To review how SARS-CoV-2 disrupts lung homeostasis and repair programs.
- To summarize current targeted and supportive therapies for COVID-19.
- To discuss the potential of cell therapy for preventing post-COVID-19 sequelae.
Main Methods:
- Literature review of SARS-CoV-2 effects on lung regeneration.
- Analysis of clinical treatments and their impact on lung repair.
- Evaluation of cell therapy strategies for COVID-19 recovery.
Main Results:
- SARS-CoV-2 infection disrupts lung homeostasis and regeneration pathways.
- Existing treatments for COVID-19 have varying effects on lung repair.
- Cell therapies, including mesenchymal stem cells, show potential but require further investigation.
Conclusions:
- Targeting lung regeneration is essential for restoring homeostasis in COVID-19 patients.
- Cell therapy offers a promising avenue for preventing post-acute sequelae of COVID-19.
- A multifaceted approach combining symptomatic treatment and regenerative strategies is needed for optimal COVID-19 patient outcomes.
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