Regenerative cell therapy for pulmonary arterial hypertension in animal models: a systematic review
Abstract Background Pulmonary arterial hypertension (PAH) is a rare disease characterized by widespread loss of the pulmonary microcirculation and elevated pulmonary arterial pressures leading to pathological right ventricular remodeling and ultimately right heart failure. Regenerative cell therapie...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-03-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-019-1172-6 |
| _version_ | 1828785755742273536 |
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| author | Colin M. Suen Duncan J. Stewart Joshua Montroy Christopher Welsh Brendan Levac Neil Wesch Alexander Zhai Dean Fergusson Lauralyn McIntyre Manoj M. Lalu |
| author_facet | Colin M. Suen Duncan J. Stewart Joshua Montroy Christopher Welsh Brendan Levac Neil Wesch Alexander Zhai Dean Fergusson Lauralyn McIntyre Manoj M. Lalu |
| author_sort | Colin M. Suen |
| collection | DOAJ |
| description | Abstract Background Pulmonary arterial hypertension (PAH) is a rare disease characterized by widespread loss of the pulmonary microcirculation and elevated pulmonary arterial pressures leading to pathological right ventricular remodeling and ultimately right heart failure. Regenerative cell therapies could potentially restore the effective lung microcirculation and provide a curative therapy for PAH. The objective of this systematic review was to compare the efficacy of regenerative cell therapies in preclinical models of PAH. Methods A systematic search strategy was developed and executed. We included preclinical animal studies using regenerative cell therapy in experimental models of PAH. Primary outcomes were right ventricular systolic pressure (RVSP) and mean pulmonary arterial pressure (mPAP). The secondary outcome was right ventricle/left ventricle + septum weight ratio (RV/LV+S). Pooled effect sizes were undertaken using random effects inverse variance models. Risk of bias and publication bias were assessed. Results The systematic search yielded 1285 studies, of which 44 met eligibility criteria. Treatment with regenerative cell therapy was associated with decreased RVSP (SMD − 2.10; 95% CI − 2.59 to − 1.60), mPAP (SMD − 2.16; 95% CI − 2.97 to − 1.35), and RV/LV+S (SMD − 1.31, 95% CI − 1.64 to − 0.97). Subgroup analysis demonstrated that cell modification resulted in greater reduction in RVSP. The effects on RVSP and mPAP remained statistically significant even after adjustment for publication bias. The majority of studies had an unclear risk of bias. Conclusions Preclinical studies of regenerative cell therapy demonstrated efficacy in animal models of PAH; however, future studies should consider incorporating design elements to reduce the risk of bias. Systematic review registration Suen CM, Zhai A, Lalu MM, Welsh C, Levac BM, Fergusson D, McIntyre L and Stewart DJ. Efficacy and safety of regenerative cell therapy for pulmonary arterial hypertension in animal models: a preclinical systematic review protocol. Syst Rev. 2016;5:89. Trial registration CAMARADES-NC3Rs Preclinical Systematic Review & Meta-analysis Facility (SyRF). http://syrf.org.uk/protocols/. Syst Rev 5:89, 2016 |
| first_indexed | 2024-12-11T23:56:40Z |
| format | Article |
| id | doaj.art-41224f9e31be479c9b01d3036d35f3a3 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-11T23:56:40Z |
| publishDate | 2019-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-41224f9e31be479c9b01d3036d35f3a32022-12-22T00:45:19ZengBMCStem Cell Research & Therapy1757-65122019-03-0110111410.1186/s13287-019-1172-6Regenerative cell therapy for pulmonary arterial hypertension in animal models: a systematic reviewColin M. Suen0Duncan J. Stewart1Joshua Montroy2Christopher Welsh3Brendan Levac4Neil Wesch5Alexander Zhai6Dean Fergusson7Lauralyn McIntyre8Manoj M. Lalu9Regenerative Medicine Program, The Ottawa Hospital Research InstituteRegenerative Medicine Program, The Ottawa Hospital Research InstituteClinical Epidemiology ProgramDepartment of Medicine, University of OttawaDepartment of Medicine, University of OttawaClinical Epidemiology ProgramRegenerative Medicine Program, The Ottawa Hospital Research InstituteClinical Epidemiology ProgramClinical Epidemiology ProgramRegenerative Medicine Program, The Ottawa Hospital Research InstituteAbstract Background Pulmonary arterial hypertension (PAH) is a rare disease characterized by widespread loss of the pulmonary microcirculation and elevated pulmonary arterial pressures leading to pathological right ventricular remodeling and ultimately right heart failure. Regenerative cell therapies could potentially restore the effective lung microcirculation and provide a curative therapy for PAH. The objective of this systematic review was to compare the efficacy of regenerative cell therapies in preclinical models of PAH. Methods A systematic search strategy was developed and executed. We included preclinical animal studies using regenerative cell therapy in experimental models of PAH. Primary outcomes were right ventricular systolic pressure (RVSP) and mean pulmonary arterial pressure (mPAP). The secondary outcome was right ventricle/left ventricle + septum weight ratio (RV/LV+S). Pooled effect sizes were undertaken using random effects inverse variance models. Risk of bias and publication bias were assessed. Results The systematic search yielded 1285 studies, of which 44 met eligibility criteria. Treatment with regenerative cell therapy was associated with decreased RVSP (SMD − 2.10; 95% CI − 2.59 to − 1.60), mPAP (SMD − 2.16; 95% CI − 2.97 to − 1.35), and RV/LV+S (SMD − 1.31, 95% CI − 1.64 to − 0.97). Subgroup analysis demonstrated that cell modification resulted in greater reduction in RVSP. The effects on RVSP and mPAP remained statistically significant even after adjustment for publication bias. The majority of studies had an unclear risk of bias. Conclusions Preclinical studies of regenerative cell therapy demonstrated efficacy in animal models of PAH; however, future studies should consider incorporating design elements to reduce the risk of bias. Systematic review registration Suen CM, Zhai A, Lalu MM, Welsh C, Levac BM, Fergusson D, McIntyre L and Stewart DJ. Efficacy and safety of regenerative cell therapy for pulmonary arterial hypertension in animal models: a preclinical systematic review protocol. Syst Rev. 2016;5:89. Trial registration CAMARADES-NC3Rs Preclinical Systematic Review & Meta-analysis Facility (SyRF). http://syrf.org.uk/protocols/. Syst Rev 5:89, 2016http://link.springer.com/article/10.1186/s13287-019-1172-6Meta-analysisPulmonary hypertensionCell therapyAnimal models of human disease |
| spellingShingle | Colin M. Suen Duncan J. Stewart Joshua Montroy Christopher Welsh Brendan Levac Neil Wesch Alexander Zhai Dean Fergusson Lauralyn McIntyre Manoj M. Lalu Regenerative cell therapy for pulmonary arterial hypertension in animal models: a systematic review Stem Cell Research & Therapy Meta-analysis Pulmonary hypertension Cell therapy Animal models of human disease |
| title | Regenerative cell therapy for pulmonary arterial hypertension in animal models: a systematic review |
| title_full | Regenerative cell therapy for pulmonary arterial hypertension in animal models: a systematic review |
| title_fullStr | Regenerative cell therapy for pulmonary arterial hypertension in animal models: a systematic review |
| title_full_unstemmed | Regenerative cell therapy for pulmonary arterial hypertension in animal models: a systematic review |
| title_short | Regenerative cell therapy for pulmonary arterial hypertension in animal models: a systematic review |
| title_sort | regenerative cell therapy for pulmonary arterial hypertension in animal models a systematic review |
| topic | Meta-analysis Pulmonary hypertension Cell therapy Animal models of human disease |
| url | http://link.springer.com/article/10.1186/s13287-019-1172-6 |
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