Mesenchymal Stromal Cells to Regenerate Emphysema: On the Horizon?

Abstract

Mesenchymal stem or stromal cells (MSCs) are multipotent cells that play a pivotal role in various phases of lung development and lung homeostasis, and potentially also lung regeneration. MSCs do not only self-renew and differentiate into renew tissues, but also have anti-inflammatory and paracrine properties to reduce damage and to support tissue regeneration, constituting a promising cell-based treatment strategy for the repair of damaged alveolar tissue in emphysema. This review discusses the current state of the art regarding the potential of MSCs for the treatment of emphysema. The optimism regarding this treatment strategy is supported by promising results from animal models. Still, there are considerable challenges before effective stem cell treatment can be realized in emphysema patients. It is difficult to draw definitive conclusions from the available animal studies, as different models, dosage protocols, administration routes, and sources of MSCs have been used with different measures of effectiveness. Moreover, the regrowth potential of differentiated tissues and organs differs between species. Essential questions about MSC engraftment, retention, and survival have not been sufficiently addressed in a systematic manner. Few human studies have investigated MSC treatment for chronic obstructive pulmonary disease, demonstrating short-term safety but no convincing benefits on clinical outcomes. Possible explanations for the lack of beneficial effects on clinical outcomes could be the source (bone marrow), route, dosage, frequency of administration, and delivery (lack of a bioactive scaffold). This review will provide a comprehensive overview of the (pre)clinical studies on MSC effects in emphysema and discuss the current challenges regarding the optimal use of MSCs for cell-based therapies.

Bone Marrow-Derived Mesenchymal Stromal Cells (MSCs) Modulate the Inflammatory Character of Alveolar Macrophages from Sarcoidosis Patients

“…The use of MSCs in humans with pulmonary diseases has recently been reviewed [38,39]. We hypothesized that MSC cellular therapy, as a local treatment through the airways, might decrease lung inflammation in patients with sarcoidosis.…”

Mesenchymal Stromal Cell Secretome for Severe COVID-19 Infections: Premises for the Therapeutic Use

“…Overall, plenty of preclinical studies have provided congruent and convincing evidence of MSC therapy effectiveness in treating many lung disorders. As recently reviewed, treatment with MSCs improved disease-associated parameters in acute respiratory distress syndrome (ARDS) [11] as well as bronchopulmonary dysplasia, chronic obstructive pulmonary disease, pulmonary hypertension and idiopathic pulmonary fibrosis [12][13][14][15]. To date, only two papers have considered MSCs for the treatment of COVID-19 pneumonia.…”

Terapia celular com células estromais mesenquimais alogênicas e xenogênicas em modelo experimental de enfisema pulmonar induzido por elastase ou fumaça de cigarro

“…The protocol for induction of pulmonary emphysema by intratracheal instillation of elastase did not allow the morphological and functional detection of the disease. Likewise, it was not possible to verify the therapeutic efficacy of ASCs in the pulmonary parenchyma of these animals after the HIRSCH; HERMANN, 2017;GOLD, 2017;HE et al, 2015;JARDIM et al, 2007;KRUK et al, 2018;RIBEIRO-PAES et al, 2009).…”

“…A limitação crônica de troca gasosa característica da DPOC é causado pela combinação da bronquiolite com o enfisema, sendo que a contribuição de cada um dos agentes causadores varia de pessoa para pessoa e podem ocorrer ou não concomitantemente (ANTUNES; SILVA; ROCCO, 2017;RAHMAN et al, 2017;GOLD, 2017;KRUK et al, 2018;MATTOS et al, 2009). A inflamação crônica pulmonar acarreta mudanças estruturais, estreitamento das vias aéreas e destruição do parênquima (BARNES;SHAPIRO;PAUWELS, 2003;FARIA et al, 2012;GOLD, 2017;JARDIM et al, 2007;RIBEIRO-PAES et al, 2009;SAETTA et al, 2001).…”

“…A DPOC pode ser entendida como uma doença sistêmica com várias comorbidades que acompanham a doença de base, e que estão associadas aos mesmos fatores de risco (tabagismo, envelhecimento, inatividade etc. O principal fator de risco para o enfisema pulmonar é a prática do tabagismo (GOLD, 2017;HE et al, 2015;KIM et al, 2015;KRUK et al, 2018;LONGHINI-DOS-SANTOS et al, 2018;MATTOS et al, 2009;RAHMAN et al, 2017;WHO, 2008 ROCCO, 2017;CHAPMAN et al, 2011;CHENG et al, 2017;FARIA et al, 2012;FREITAS, 2009;LONGHINI-DOS-SANTOS, 2014;MAGNUSSEN et al, 2014. OLIVEIRA et al, 2013KLOOSTER et al, 2015, RIBEIRO-PAES et al, 2009 (MARCELINO et al, 2014;RAHMAN et al, 2017;RIBEIRO-PAES et al, 2012;SHAPIRO, 2000;WRIGHT et al, 2008).…”