Potential Therapeutic Strategy in Chronic Obstructive Pulmonary Disease Using Pioglitazone-Augmented Wharton's Jelly-Derived Mesenchymal Stem Cells

Abstract

BackgroundA recent study reported that mesenchymal stem cells possess potential cellular therapeutic properties for treating patients with chronic obstructive pulmonary disease, which is characterized by emphysema. We examined the potential therapeutic effect of Wharton's Jelly-derived mesenchymal stem cells (WJMSCs), following pretreatment with pioglitazone, in lung regeneration mouse emphysema models.MethodsWe used two mouse emphysema models, an elastase-induced model and a cigarette smoke-induced model. We intravenously injected WJMSCs (1×104/mouse) to mice, pretreated or not, with pioglitazone for 7 days. We measured the emphysema severity by mean linear intercepts (MLI) analysis using lung histology.ResultsPioglitazone pretreated WJMSCs (pioWJMSCs) were associated with greater lung regeneration than non-augmented WJMSCs in the two mouse emphysema models. In the elastase-induced emphysema model, the MLIs were 59.02±2.42 µm (n=6), 72.80±2.87 µm (n=6), for pioWJMSCs injected mice, and non-augmented WJMSCs injected mice, respectively (p<0.01). Both pioWJMSCs and non-augmented WJMSCs showed regenerative effects in the cigarette smoke emphysema model (MLIs were 41.25±0.98 [n=6] for WJMSCs and38.97±0.61 µm [n=6] for pioWJMSCs) compared to smoking control mice (51.65±1.36 µm, n=6). The mean improvement of MLI appeared numerically better in pioWJMSCs than in non-augmented WJMSCs injected mice, but the difference did not reach the level of statistical significance (p=0.071).ConclusionPioWJMSCs may produce greater lung regeneration, compared to non-augmented WJMSCs, in a mouse emphysema model.

An overview of mesenchymal stem cells and their potential therapeutic benefits in cancer therapy (Review)

“…For example, MSCs were reported to enhance the therapeutic capabilities of tendon repair when pretreated with pioglitazone (196). Other studies using pioglitazone as the priming agent also found similar results, where pretreated MSCs had greater therapeutic effects on lung regeneration in an emphysema mouse model (197,198). Pioglitazone has been administered indirectly to breast cancer cells via stem-and-cancer cell interaction (199).…”

Pioglitazone and Risk of Chronic Obstructive Pulmonary Disease in Patients with Type 2 Diabetes Mellitus: A Retrospective Cohort Study

“…23 Pioglitazone can reduce sepsis-induced lung injury by reducing inflammation 19 and potentiate the repair of lung injury by mesenchymal stem cells. 20,21 Therefore, the mechanisms of a lower risk of COPD might be related to an upregulation and activation of PPARγ and the subsequent anti-inflammatory effects and injury repair capability of pioglitazone.…”

“…Pioglitazone effectively prevents sepsis-induced lung injury in mice by reducing inflammation. 19 In emphysema mouse models, pioglitazone-pretreated adipose-derived mesenchymal stem cells 20 and Wharton's Jelly-derived mesenchymal stem cells 21 were more potent in the repair of lung injury. In in vitro and in vivo models of COPD, TZDs, including rosiglitazone, pioglitazone and ciglitazone, attenuated pulmonary inflammation.…”

Bone marrow stem cells therapy alleviates vascular injury in a chronic obstructive pulmonary disease‑obstructive sleep apnea overlap syndrome rat model

“…BMSCs can quickly migrate from the BM into the peripheral circulation, mobilize to injury sites and differentiate into EPCs that further differentiate into VECs to repair the injury ( 21 ). MSCs have potential therapeutic roles in the treatment of obstructive sleep apnea-hypopnea syndrome (OSAHS) ( 22 ) and COPD ( 23 , 24 ). Previous studies have revealed that BMSCs can differentiate into alveolar epithelial cells in animals with lung injury and can repair pathological tissue ( 25 , 26 ).…”