Heba M. Saad Eldien, H. Abdel-Aziz, D. Sayed, W. Mubarak, H. H. Hareedy, S. Mansor, Toshiko Yoshida, M. Fathy
Background Human adipose tissue-derived mesenchymal stromal cells (AD-MSCs) have been under focus in regenerative medicine since their discovery as a suitable source of MSCs. AD-MSCs are heterogeneous cells and exhibit variations in population doubling time, morphology and proliferative capacity. This study investigated if human AD-MSCs are developing, during in vitro long-term cultivation, in an unwanted or aberrant way. Methods This study monitored AD-MSCs during their in vitro culture till the tenth passage investigating proliferation kinetics, DNA index and surface markers expression. Also, periostin gene expression was examined. Results The proliferation capacity and colony forming unit were decreased after passage 6 and the population doubling time was increased. Flow cytometric analysis revealed that newly cultivated population strongly expressed MSCs markers, furthermore, reduction of CD105 expression appeared in passage 5 onwards, the later was associated with significant increase in expression of CD34 (a hematopoietic cell marker). Also, reduction of CD73 and CD90 expression was observed from passage 8. Furthermore, during the first six passages, periostin expression was significantly unchanged, with significant upregulation in late passages. Conclusions Long-term cultivation of human AD-MSCs changed their characters in an aberrant way and the first four passages might be the most appropriate passages for therapy. More investigation and understanding of these variations are needed to help in standardizing the expansion of MSCs-based therapies.
{"title":"Periostin expression and characters of human adipose tissue-derived mesenchymal stromal cells were aberrantly affected by in vitro cultivation.","authors":"Heba M. Saad Eldien, H. Abdel-Aziz, D. Sayed, W. Mubarak, H. H. Hareedy, S. Mansor, Toshiko Yoshida, M. Fathy","doi":"10.21037/sci.2019.08.09","DOIUrl":"https://doi.org/10.21037/sci.2019.08.09","url":null,"abstract":"Background\u0000Human adipose tissue-derived mesenchymal stromal cells (AD-MSCs) have been under focus in regenerative medicine since their discovery as a suitable source of MSCs. AD-MSCs are heterogeneous cells and exhibit variations in population doubling time, morphology and proliferative capacity. This study investigated if human AD-MSCs are developing, during in vitro long-term cultivation, in an unwanted or aberrant way.\u0000\u0000\u0000Methods\u0000This study monitored AD-MSCs during their in vitro culture till the tenth passage investigating proliferation kinetics, DNA index and surface markers expression. Also, periostin gene expression was examined.\u0000\u0000\u0000Results\u0000The proliferation capacity and colony forming unit were decreased after passage 6 and the population doubling time was increased. Flow cytometric analysis revealed that newly cultivated population strongly expressed MSCs markers, furthermore, reduction of CD105 expression appeared in passage 5 onwards, the later was associated with significant increase in expression of CD34 (a hematopoietic cell marker). Also, reduction of CD73 and CD90 expression was observed from passage 8. Furthermore, during the first six passages, periostin expression was significantly unchanged, with significant upregulation in late passages.\u0000\u0000\u0000Conclusions\u0000Long-term cultivation of human AD-MSCs changed their characters in an aberrant way and the first four passages might be the most appropriate passages for therapy. More investigation and understanding of these variations are needed to help in standardizing the expansion of MSCs-based therapies.","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":"6 1","pages":"33"},"PeriodicalIF":0.0,"publicationDate":"2019-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.21037/sci.2019.08.09","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42069949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Conversion of one cell type to another by reprogramming offers valuable opportunities for disease modeling and regenerative medicine. In a much-anticipated scenario, tissues generated from reprogrammed cells will be used to replace degenerated or lost tissues in patients suffering from injury or diseases such as Alzheimer’s, which causes loss of functional nerve cells (neurons) in the brain.
{"title":"CRISPR-activation-based screen reveals neuronal fate promotion by polycomb repressive complex 2 during direct reprogramming.","authors":"Tim Wolfram, B. Tursun","doi":"10.21037/sci.2019.08.04","DOIUrl":"https://doi.org/10.21037/sci.2019.08.04","url":null,"abstract":"Conversion of one cell type to another by reprogramming offers valuable opportunities for disease modeling and regenerative medicine. In a much-anticipated scenario, tissues generated from reprogrammed cells will be used to replace degenerated or lost tissues in patients suffering from injury or diseases such as Alzheimer’s, which causes loss of functional nerve cells (neurons) in the brain.","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":"6 1","pages":"32"},"PeriodicalIF":0.0,"publicationDate":"2019-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.21037/sci.2019.08.04","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46063363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background Usher syndrome is the most common form of syndromic retinitis pigmentosa and includes types I, II, and III with varying degrees of hearing loss. We present results of 10 eyes with Usher syndrome treated with autologous bone marrow derived stem cells (BMSC) within the Stem Cell Ophthalmology Treatment Study (SCOTS). Methods Preoperative Snellen visual acuities ranged from 20/30-1 to 20/400 with the average pre-operative Snellen acuity approximately 20/85 and the average logarithm of the minimum angle of resolution (LogMAR) acuity 0.635. All eyes had significantly impaired visual fields and patients reported hearing loss as part of this syndromic retinitis pigmentosa. Treatment using the protocols of the SCOTS study using BMSC provided by retrobulbar, subtenons, intravitreal and intravenous injections. Results Following treatment, 80% of the Usher eyes showed an improvement in visual acuity. Of the eyes that improved the average increase in visual acuity was 36.4% on LogMAR with improvements ranging from 23% to 94%. The average post-operative change in all treated eyes was a gain of 0.18 LogMAR and an increase in visual acuity of 28.3% on LogMAR. The results showed high statistical significance with P<0.001. Visual fields generally improved. No patient experienced a loss of vision. One patient underwent preoperative and 4-month post-operative audiometry testing which demonstrated improvement. The procedures were performed safely and without complications. Conclusions Findings confirm meaningful improvement in visual acuity is possible in Usher syndrome using BMSC protocols developed in the SCOTS study. Statistical significance and safety were established.
{"title":"Stem Cell Ophthalmology Treatment Study (SCOTS): bone marrow derived stem cells in the treatment of Usher syndrome.","authors":"J. Weiss, S. Lévy","doi":"10.21037/sci.2019.08.07","DOIUrl":"https://doi.org/10.21037/sci.2019.08.07","url":null,"abstract":"Background\u0000Usher syndrome is the most common form of syndromic retinitis pigmentosa and includes types I, II, and III with varying degrees of hearing loss. We present results of 10 eyes with Usher syndrome treated with autologous bone marrow derived stem cells (BMSC) within the Stem Cell Ophthalmology Treatment Study (SCOTS).\u0000\u0000\u0000Methods\u0000Preoperative Snellen visual acuities ranged from 20/30-1 to 20/400 with the average pre-operative Snellen acuity approximately 20/85 and the average logarithm of the minimum angle of resolution (LogMAR) acuity 0.635. All eyes had significantly impaired visual fields and patients reported hearing loss as part of this syndromic retinitis pigmentosa. Treatment using the protocols of the SCOTS study using BMSC provided by retrobulbar, subtenons, intravitreal and intravenous injections.\u0000\u0000\u0000Results\u0000Following treatment, 80% of the Usher eyes showed an improvement in visual acuity. Of the eyes that improved the average increase in visual acuity was 36.4% on LogMAR with improvements ranging from 23% to 94%. The average post-operative change in all treated eyes was a gain of 0.18 LogMAR and an increase in visual acuity of 28.3% on LogMAR. The results showed high statistical significance with P<0.001. Visual fields generally improved. No patient experienced a loss of vision. One patient underwent preoperative and 4-month post-operative audiometry testing which demonstrated improvement. The procedures were performed safely and without complications.\u0000\u0000\u0000Conclusions\u0000Findings confirm meaningful improvement in visual acuity is possible in Usher syndrome using BMSC protocols developed in the SCOTS study. Statistical significance and safety were established.","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":"6 1","pages":"31"},"PeriodicalIF":0.0,"publicationDate":"2019-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.21037/sci.2019.08.07","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45479147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
It is still one of the most intriguing questions in biology, how the multitudes of cell types a single organism possesses, are adequately born during development. It is clear that there are transcription factors with sufficient activity to drive cells towards specific cell identities, however to date the known genes are limited to a handful of linages (e.g., pluripotency, neurogenesis, β-cell development, etc.) and even in these cases we are far from a comprehensive understanding of contributing factors and molecular mechanisms.
{"title":"Seeking fate-CRISPRa screens reveal new neural lineage and reprogramming factors.","authors":"Valentin Baumann, S. Stricker","doi":"10.21037/sci.2019.08.03","DOIUrl":"https://doi.org/10.21037/sci.2019.08.03","url":null,"abstract":"It is still one of the most intriguing questions in biology, how the multitudes of cell types a single organism possesses, are adequately born during development. It is clear that there are transcription factors with sufficient activity to drive cells towards specific cell identities, however to date the known genes are limited to a handful of linages (e.g., pluripotency, neurogenesis, β-cell development, etc.) and even in these cases we are far from a comprehensive understanding of contributing factors and molecular mechanisms.","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":"6 1","pages":"30"},"PeriodicalIF":0.0,"publicationDate":"2019-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.21037/sci.2019.08.03","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49192458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cellular differentiation is the process by which unspecialized cells mature into a variety of functional cell types to form the tissues of a multicellular organism. This specialization occurs during embryonic development when a single zygote gives rise to different cell types and in adulthood when reservoirs of stem cells differentiate to replace senescent or damaged cells.
{"title":"SETD7 in cardiomyocyte differentiation and cardiac function.","authors":"T. Basuroy, I. L. de la Serna","doi":"10.21037/sci.2019.08.01","DOIUrl":"https://doi.org/10.21037/sci.2019.08.01","url":null,"abstract":"Cellular differentiation is the process by which unspecialized cells mature into a variety of functional cell types to form the tissues of a multicellular organism. This specialization occurs during embryonic development when a single zygote gives rise to different cell types and in adulthood when reservoirs of stem cells differentiate to replace senescent or damaged cells.","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":"6 1","pages":"29"},"PeriodicalIF":0.0,"publicationDate":"2019-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.21037/sci.2019.08.01","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47032719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Dragani, G. Andreani, C. Fava, F. Daraio, E. Gottardi, E. Giugliano, P. Nicoli, G. Rege‐Cambrin
Philadelphia positive acute lymphoblastic leukemia is well documented nowadays but very little is known about Philadelphia positive lymphoblastic lymphoma (LBL). Only two cases are available in literature and both of them died during treatment whereas the patient treated in our center is still alive 3 years after the initial diagnosis. A chemo-free regimen was used in induction with dasatinib plus steroids with local radiotherapy on the mass, and then the patient underwent bone marrow transplant. Philadelphia positive lymphoblastic lymphoma is a difficult diagnosis to make and the management of this extremely rare disease is very challenging.
{"title":"Philadelphia-positive lymphoblastic lymphoma: a case report and review of the literature.","authors":"M. Dragani, G. Andreani, C. Fava, F. Daraio, E. Gottardi, E. Giugliano, P. Nicoli, G. Rege‐Cambrin","doi":"10.21037/SCI.2019.06.06","DOIUrl":"https://doi.org/10.21037/SCI.2019.06.06","url":null,"abstract":"Philadelphia positive acute lymphoblastic leukemia is well documented nowadays but very little is known about Philadelphia positive lymphoblastic lymphoma (LBL). Only two cases are available in literature and both of them died during treatment whereas the patient treated in our center is still alive 3 years after the initial diagnosis. A chemo-free regimen was used in induction with dasatinib plus steroids with local radiotherapy on the mass, and then the patient underwent bone marrow transplant. Philadelphia positive lymphoblastic lymphoma is a difficult diagnosis to make and the management of this extremely rare disease is very challenging.","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":"6 1","pages":"17"},"PeriodicalIF":0.0,"publicationDate":"2019-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.21037/SCI.2019.06.06","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47232362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
W. Roque, A. Rehman, G. Suero-Abreu, B. Danek, Joseph Colao, Alla Fayngersh, S. Srinivas, J. Kra, D. Cai, V. Chang
Tumor lysis syndrome (TLS) refers to a constellation of metabolic abnormalities that result from release of intracellular solutes (potassium, phosphate, and nucleic acid metabolites) from rapidly dying tumor cells. While TLS most commonly occurs following chemotherapy, spontaneous TLS can rarely occur in rapidly dividing liquid or solid malignancies. Here, we report the cases of two patients who presented with non-specific symptoms and were found to have spontaneous TLS. Work-up in both cases led to a diagnosis of T-cell malignancy (i.e., acute lymphoblastic leukemia and angioimmunoblastic lymphoma). Given that spontaneous TLS can be the first manifestation of an underlying malignancy, all physicians should be familiar with this oncologic emergency. Early recognition and prompt management can be lifesaving for patients with an otherwise curable malignancy.
{"title":"Spontaneous tumor lysis syndrome in T-cell malignancy: two case reports.","authors":"W. Roque, A. Rehman, G. Suero-Abreu, B. Danek, Joseph Colao, Alla Fayngersh, S. Srinivas, J. Kra, D. Cai, V. Chang","doi":"10.21037/SCI.2019.07.01","DOIUrl":"https://doi.org/10.21037/SCI.2019.07.01","url":null,"abstract":"Tumor lysis syndrome (TLS) refers to a constellation of metabolic abnormalities that result from release of intracellular solutes (potassium, phosphate, and nucleic acid metabolites) from rapidly dying tumor cells. While TLS most commonly occurs following chemotherapy, spontaneous TLS can rarely occur in rapidly dividing liquid or solid malignancies. Here, we report the cases of two patients who presented with non-specific symptoms and were found to have spontaneous TLS. Work-up in both cases led to a diagnosis of T-cell malignancy (i.e., acute lymphoblastic leukemia and angioimmunoblastic lymphoma). Given that spontaneous TLS can be the first manifestation of an underlying malignancy, all physicians should be familiar with this oncologic emergency. Early recognition and prompt management can be lifesaving for patients with an otherwise curable malignancy.","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":"6 1","pages":"24"},"PeriodicalIF":0.0,"publicationDate":"2019-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.21037/SCI.2019.07.01","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46265784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer is a genetic disease which results in a functional imbalance between tumour-repressive and oncogenic signals. The WHO highlights the burden of this indomitable disease, listing it as the second leading cause of death globally. The major cause of cancer-related death is rarely the effect of the primary tumour itself, but rather, the devastating spread of cancer cells in metastases. Epithelial-mesenchymal plasticity (EMP)-termed as the ability of cells to maintain its plasticity and transit between epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) states-plays a fundamental role in cancer metastasis. These cell transitions allow them migrate from the primary tumour and invade the secondary site. EMP is associated with migration, invasion, colonisation, self-renewal and drug resistance. This review briefly elucidates the mechanism of EMP and the association between cancer stem cells (CSCs) and circulating tumour cells (CTCs), biomarkers and signalling pathways involved in EMP as well as drug resistance and therapeutic targeting.
{"title":"Epithelial-mesenchymal plasticity-engaging stemness in an interplay of phenotypes.","authors":"V. Chin, C. Lim","doi":"10.21037/SCI.2019.08.08","DOIUrl":"https://doi.org/10.21037/SCI.2019.08.08","url":null,"abstract":"Cancer is a genetic disease which results in a functional imbalance between tumour-repressive and oncogenic signals. The WHO highlights the burden of this indomitable disease, listing it as the second leading cause of death globally. The major cause of cancer-related death is rarely the effect of the primary tumour itself, but rather, the devastating spread of cancer cells in metastases. Epithelial-mesenchymal plasticity (EMP)-termed as the ability of cells to maintain its plasticity and transit between epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) states-plays a fundamental role in cancer metastasis. These cell transitions allow them migrate from the primary tumour and invade the secondary site. EMP is associated with migration, invasion, colonisation, self-renewal and drug resistance. This review briefly elucidates the mechanism of EMP and the association between cancer stem cells (CSCs) and circulating tumour cells (CTCs), biomarkers and signalling pathways involved in EMP as well as drug resistance and therapeutic targeting.","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":"6 1","pages":"25"},"PeriodicalIF":0.0,"publicationDate":"2019-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.21037/SCI.2019.08.08","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41819541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fereshte Nejaddehbashi, V. Bayati, L. Mashali, M. Hashemitabar, M. Abbaspour, E. Moghimipour, M. Orazizadeh
Background The purpose of this study was to introduce an applicable culture technique to isolate human dermal fibroblasts (HDFs); which could also contribute to research, clinical practices, as well as tissue engineering. Methods Samples from the human skin were dissected and cultured via serial explant technique. Subsequently, the isolated fibroblasts were assessed for their protein markers and genetic variations via immunofluorescence (IF) and karyotyping; respectively. Following the employment of this technique, a small piece of explant completely disappeared; while no dermis remained after 10 days. Results The quantity of HDFs harvested through this culture technique was reported at a normal level. The results of immunostaining also indicated that the isolated fibroblasts had expressed vimentin and fibronectin; whereas no cells had shown cytokeratin and epidermal marker. Moreover, karyotyping results for the fibroblasts isolated by the given technique revealed no chromosomal diversity after passage 20. Conclusions It was concluded that serial explant culture was an efficient technique for isolating HDFs from a small piece of skin in short-time periods; which could also preserve their normal morphology and molecular characteristics.
{"title":"Isolating human dermal fibroblasts using serial explant culture.","authors":"Fereshte Nejaddehbashi, V. Bayati, L. Mashali, M. Hashemitabar, M. Abbaspour, E. Moghimipour, M. Orazizadeh","doi":"10.21037/SCI.2019.08.05","DOIUrl":"https://doi.org/10.21037/SCI.2019.08.05","url":null,"abstract":"Background\u0000The purpose of this study was to introduce an applicable culture technique to isolate human dermal fibroblasts (HDFs); which could also contribute to research, clinical practices, as well as tissue engineering.\u0000\u0000\u0000Methods\u0000Samples from the human skin were dissected and cultured via serial explant technique. Subsequently, the isolated fibroblasts were assessed for their protein markers and genetic variations via immunofluorescence (IF) and karyotyping; respectively. Following the employment of this technique, a small piece of explant completely disappeared; while no dermis remained after 10 days.\u0000\u0000\u0000Results\u0000The quantity of HDFs harvested through this culture technique was reported at a normal level. The results of immunostaining also indicated that the isolated fibroblasts had expressed vimentin and fibronectin; whereas no cells had shown cytokeratin and epidermal marker. Moreover, karyotyping results for the fibroblasts isolated by the given technique revealed no chromosomal diversity after passage 20.\u0000\u0000\u0000Conclusions\u0000It was concluded that serial explant culture was an efficient technique for isolating HDFs from a small piece of skin in short-time periods; which could also preserve their normal morphology and molecular characteristics.","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":"6 1","pages":"23"},"PeriodicalIF":0.0,"publicationDate":"2019-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.21037/SCI.2019.08.05","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42880446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-16eCollection Date: 2019-01-01DOI: 10.21037/sci.2019.06.09
Qi Lu, Ahmed H K El-Hashash
Idiopathic pulmonary fibrosis (IPF) is an example of interstitial lung diseases that is characterized by chronic, progressive, and fibrotic lung injuries. During lung fibrosis, normal healthy lung tissues are replaced by remarkably destroyed alveolar architecture and altered extracellular cell matrix. These changes eventually cause severe disruption of the tightly-controlled gas exchange process and reduction of lung compliance that ultimately lead to both respiratory failure and death. In the last decade, progress has been made toward understanding the pathogenesis of pulmonary fibrosis, and two novel disease-modifying therapies were approved. However, finding more effective treatments for pulmonary fibrosis is still a challenge, with its incidence continues to increase globally, which is associated with significantly high mortality, morbidity and economical healthcare burden. Different stem cell types have recently emerged as a promising therapy for human diseases, including lung fibrosis, with numerous studies on the identification, characterization, proliferation and differentiation of stem cells. A large body of both basic and pre-clinical research on stem cells has been recently translated to patient care worldwide. Herein, we review recent advances in our understanding of the pathophysiology of IPF, and types of cells used in IPF cell-based therapies, including alveolar and mixed lung epithelial cells, different stem cell types (MSCs, ADSCs, IPSCs…etc.), endogenous lung tissue-specific stem cells, and circulating endothelial progenitors (EPCs). We also discuss recent studies on the applications of these cells in IPF therapy and their delivery routes, effective doses for cell therapy, and timing of delivery. Finally, we discuss attractive recent and current clinical trials conducted on cell-based therapy for IPF.
{"title":"Cell-based therapy for idiopathic pulmonary fibrosis.","authors":"Qi Lu, Ahmed H K El-Hashash","doi":"10.21037/sci.2019.06.09","DOIUrl":"10.21037/sci.2019.06.09","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is an example of interstitial lung diseases that is characterized by chronic, progressive, and fibrotic lung injuries. During lung fibrosis, normal healthy lung tissues are replaced by remarkably destroyed alveolar architecture and altered extracellular cell matrix. These changes eventually cause severe disruption of the tightly-controlled gas exchange process and reduction of lung compliance that ultimately lead to both respiratory failure and death. In the last decade, progress has been made toward understanding the pathogenesis of pulmonary fibrosis, and two novel disease-modifying therapies were approved. However, finding more effective treatments for pulmonary fibrosis is still a challenge, with its incidence continues to increase globally, which is associated with significantly high mortality, morbidity and economical healthcare burden. Different stem cell types have recently emerged as a promising therapy for human diseases, including lung fibrosis, with numerous studies on the identification, characterization, proliferation and differentiation of stem cells. A large body of both basic and pre-clinical research on stem cells has been recently translated to patient care worldwide. Herein, we review recent advances in our understanding of the pathophysiology of IPF, and types of cells used in IPF cell-based therapies, including alveolar and mixed lung epithelial cells, different stem cell types (MSCs, ADSCs, IPSCs…etc.), endogenous lung tissue-specific stem cells, and circulating endothelial progenitors (EPCs). We also discuss recent studies on the applications of these cells in IPF therapy and their delivery routes, effective doses for cell therapy, and timing of delivery. Finally, we discuss attractive recent and current clinical trials conducted on cell-based therapy for IPF.</p>","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":"6 1","pages":"22"},"PeriodicalIF":0.0,"publicationDate":"2019-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6737434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44768440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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