AbstractHuman lungs bear their own reservoir of endogenous mesenchymal stem cells (MSCs). Although described as located perivascular, the cellular identity of primary lung MSCs remains elusive. Here we investigated the vascular nature of lung-resident MSCs (LR-MSCs) using healthy human lung tissue. LR-MSCs predominately reside within the vascular stem cell niche, the so-called vasculogenic zone of adult lung arteries. Primary LR-MSCs isolated from normal human lung tissue showed typical MSC characteristics in vitro and were phenotypically and functionally indistinguishable from MSCs derived from the vascular wall of adult human blood vessels (VW-MSCs). Moreover, LR-MSCs expressed the VW-MSC-specific HOX code a characteristic to discriminate VW-MSCs from phenotypical similar cells. Thus, LR-MSC should be considered as VW-MSCs. Immunofluorescent analyses of non-small lung cancer (NSCLC) specimen further confirmed the vascular adventitia as stem cell niche for LR-MSCs, and revealed their mobilization and activation in NSCLC progression. These findings have implications for understanding the role of MSC in normal lung physiology and pulmonary diseases, as well as for the rational design of additional therapeutic approaches.

01 Dec 2019·Stem Cell ResearchQ4 · MEDICINE

Simulated microgravity-cultured mesenchymal stem cells improve recovery following spinal cord ischemia in rats

Q4 · MEDICINE

ArticleOA

Author: Takahashi, Shinya ; Otsuka, Takashi ; Yuge, Louis ; Imura, Takeshi ; Kurose, Tomoyuki ; Nakagawa, Kei ; Sueda, Taijiro

Spinal cord ischemia is a potential complication of thoracoabdominal aortic surgery that may induce irreversible motor disability. We investigated the therapeutic efficacy of simulated microgravity-cultured mesenchymal stem cell (MSC) injection following spinal cord ischemia-reperfusion injury. Sprague-Dawley rats were divided into sham, phosphate-buffered saline (PBS), normal gravity-cultured MSC (MSC-1 G), and simulated microgravity-cultured MSC (MSC-MG) groups. Spinal cord ischemia was induced by transient balloon occlusion of the thoracic aorta, which was followed immediately by PBS or MSC injection into the left carotid artery. Hindlimb motor function was evaluated by the Basso-Beattie-Bresnahan (BBB) scale. Spinal cords were removed 1, 3, or 7 days post-injury for immunohistochemical staining and Western blot analysis. One day post-injury, a few infiltrating inflammatory cells and small vacuoles were observed without significant group differences, followed over several days by progressive spinal cord degeneration. Glial fibrillary acidic protein (GFAP)-positive (reactive) astrocyte numbers were increased in all three groups, and brain-derived neurotrophic factor (BDNF) was colocalized with GFAP-positive cells in spinal ventral horn. Animals in the MSC-MG group demonstrated greater BDNF-positive astrocyte numbers, reduced caspase-3-positive cell numbers, and superior motor recovery. Microgravity-cultured MSC-based therapy may improve functional recovery following spinal ischemia-reperfusion injury by promoting astrocytic BDNF release, thereby preventing apoptosis.

01 Nov 2015·Cell Stress and ChaperonesQ3 · BIOLOGY

Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol alleviates elastase-induced emphysema in a mouse model

Q3 · BIOLOGY

Article

Author: Huang, Tsung-Teng ; Lee, Hsuan-Shu ; Chen, Young-Bin ; Cheng, Winston T K ; Choo, Kong-Bung ; Lan, Ying-Wei ; Chong, Kowit-Yu ; Chen, Lih-Geeng

Chronic obstructive pulmonary disease (COPD) is a sustained blockage of the airways due to lung inflammation occurring with chronic bronchitis and/or emphysema. Progression of emphysema may be slowed by vascular endothelial growth factor A (VEGFA), which reduces apoptotic tissue depletion. Previously, authors of the present report demonstrated that cis-resveratrol (c-RSV)-induced heat-shock protein 70 (HSP70) promoter-regulated VEGFA expression promoted neovascularization of genetically modified mesenchymal stem cells (HSP-VEGFA-MSC) in a mouse model of ischemic disease. Here, this same stem cell line was evaluated for its protective capacity to alleviate elastase-induced pulmonary emphysema in mice. Results of this study showed that c-RSV-treatment of HSP-VEGFA-MSC exhibited synergy between HSP70 transcription activity and induced expression of anti-oxidant-related genes when challenged by cigarette smoke extracts. Eight weeks after jugular vein injection of HSP-VEGFA-MSC into mice with elastase-induced pulmonary emphysema followed by c-RSV treatment to induce transgene expression, significant improvement was observed in respiratory functions. Expression of VEGFA, endogenous nuclear factor erythroid 2-related factor (Nrf 2), and manganese superoxide dismutase (MnSOD) was significantly increased in the lung tissues of the c-RSV-treated mice. Histopathologic examination of treated mice revealed gradual but significant abatement of emphysema and restoration of airspace volume. In conclusion, the present investigation demonstrates that c-RSV-regulated VEGFA expression in HSP-VEGFA-MSC significantly improved the therapeutic effects on the treatment of COPD in the mouse, possibly avoiding side effects associated with constitutive VEGFA expression.

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Indication	Highest Phase	Country/Location	Organization	Date
Lower limb ischemia	Preclinical	TW	Taiwan Bio Therapeutics Co., Ltd.	29 Sep 2022

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