Abstract 16158: Comparative Effects of Bone Marrow Derived versus Umbilical Cord Tissue Mesenchymal Stem Cells in an Experimental Model of Bronchopulmonary Dysplasia

Introduction: Bronchopulmonary dysplasia (BPD) or chronic lung injury of newborn is a life-threatening condition in preterm infants with few effective therapies. Mesenchymal stem cells (MSC) are a promising therapeutic strategy for BPD. The ideal MSC source for BPD prevention is however unknown. Umbilical cord tissue (UCT) MSC may potentially have more anti-inflammatory and pro-angiogenic properties. Hypothesis: We hypothesized that the UCT-MSC will have superior lung regenerative effect in BPD owing to superior anti-inflammatory and pro-angiogenic properties as compared to BM-MSC. Methods: Newborn rats (n=10-12/group) were randomly assigned to normoxia or hyperoxia (85% O 2 ) from postnatal day (P) 1 to 21 were given intra-tracheal (IT) BM or UCT-MSC (1 x 10 6 cells/50 μl), or placebo (PL) on P3. Results: Hyperoxia PL-treated pups had marked alveolar simplification, vascular rarefaction, remodeling and lung inflammation. Administration of both BM-MSC and UCT-MSC significantly improved alveolar structure, vascular density, pulmonary hypertension, vascular remodeling and lung inflammation. However, the improvement in alveolar structure and lung inflammation was more marked in hyperoxic pups who received UCT-MSC. In vitro studies demonstrated greater TSG-6 and IL-10 expression in UCT-MSC as compared to BM-MSC. Moreover, lung epithelial cells incubated with UCT-MSC conditioned media had greater wound healing following scratch injury. Conclusion: These findings demonstrate that while both BM and UCT-MSC have lung regenerative effects, UCT-MSC have greater anti-inflammatory and alveolar protective effects in experimental BPD. These findings have significant implications for cellular therapy in BPD, as it suggests that UCT-MSC are a superior cellular source for preterm lung protection.

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Anti-Inflammatory Therapeutic Development and Optimization of Umbilical Cord Tissue Derived Mesenchymal Stem Cells

Journal of Stem Cell Research & Therapy ◽

10.4172/2157-7633.1000435 ◽

2018 ◽

Vol 08 (08) ◽

Cited By ~ 1

Author(s):

Morgan T Sutton ◽

Sukhmani Kaur ◽

Katherine S Brown ◽

Matthew L Skiles ◽

Michael A Folz ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Umbilical Cord Tissue ◽

Therapeutic Development ◽

Anti Inflammatory

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Correction to: Clinical feasibility of umbilical cord tissue-derived mesenchymal stem cells in the treatment of multiple sclerosis

Journal of Translational Medicine ◽

10.1186/s12967-021-02869-4 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Neil H. Riordan ◽

Isabela Morales ◽

Giselle Fernández ◽

Nicole Allen ◽

Neal E. Fearnot ◽

...

Keyword(s):

Multiple Sclerosis ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Umbilical Cord Tissue

An amendment to this paper has been published and can be accessed via the original article.

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Consecutive daily administration of intratracheal surfactant and human umbilical cord-derived mesenchymal stem cells attenuates hyperoxia-induced lung injury in neonatal rats

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02335-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Hsiu-Chu Chou ◽

Chien-Hsiang Chang ◽

Chien-Han Chen ◽

Willie Lin ◽

Chung-Ming Chen

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Lung Injury ◽

Umbilical Cord ◽

Daily Administration ◽

Vascular Density ◽

Human Umbilical Cord ◽

Neonatal Rats ◽

Vegf Expression ◽

Intratracheal Administration

Abstract Background Surfactant therapy is a standard of care for preterm infants with respiratory distress and reduces the incidence of death and bronchopulmonary dysplasia in these patients. Our previous study found that mesenchymal stem cells (MSCs) attenuated hyperoxia-induced lung injury and the combination therapy of surfactant and human umbilical cord-derived MSCs (hUC-MSCs) did not have additive effects on hyperoxia-induced lung injury in neonatal rats. The aim is to evaluate the effects of 2 consecutive days of intratracheal administration of surfactant and hUC-MSCs on hyperoxia-induced lung injury. Methods Neonatal Sprague Dawley rats were reared in either room air (RA) or hyperoxia (85% O2) from postnatal days 1 to 14. On postnatal day 4, the rats received intratracheal injections of either 20 μL of normal saline (NS) or 20 μL of surfactant. On postnatal day 5, the rats reared in RA received intratracheal NS, and the rats reared in O2 received intratracheal NS or hUC-MSCs (3 × 104 or 3 × 105 cells). Six study groups were examined: RA + NS + NS, RA + surfactant + NS, O2 + NS + NS, O2 + surfactant + NS, O2 + surfactant + hUC-MSCs (3 × 104 cells), and O2 + surfactant + hUC-MSCs (3 × 105 cells). The lungs were excised for histological, western blot, and cytokine analyses. Results The rats reared in hyperoxia and treated with NS yielded significantly higher mean linear intercepts (MLIs) and interleukin (IL)-1β and IL-6 levels and significantly lower vascular endothelial growth factors (VEGFs), platelet-derived growth factor protein expression, and vascular density than did those reared in RA and treated with NS or surfactant. The lowered MLIs and cytokines and the increased VEGF expression and vascular density indicated that the surfactant and surfactant + hUC-MSCs (3 × 104 cells) treatment attenuated hyperoxia-induced lung injury. The surfactant + hUC-MSCs (3 × 105 cells) group exhibited a significantly lower MLI and significantly higher VEGF expression and vascular density than the surfactant + hUC-MSCs (3 × 104 cells) group did. Conclusions Consecutive daily administration of intratracheal surfactant and hUC-MSCs can be an effective regimen for treating hyperoxia-induced lung injury in neonates.

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Heterogeneity of Umbilical Cords as a Source for Mesenchymal Stem Cells

Dataset Papers in Biology ◽

10.7167/2013/370103 ◽

2013 ◽

Vol 2013 ◽

pp. 1-4 ◽

Cited By ~ 9

Author(s):

O. O. Maslova ◽

N. S. Shuvalova ◽

O. M. Sukhorada ◽

S. M. Zhukova ◽

O. G. Deryabina ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Umbilical Cord ◽

Optimal Conditions ◽

Umbilical Cord Tissue ◽

Umbilical Cords

The object of the paper is to show the heterogeneity of 300 cord samples processed in the current research. The differences in effectiveness of mesenchymal stem cell (MSC) isolation are shown. Moreover, the recommendations for choosing the method of MSC isolation depending on the value of stromal-vascular rate are given. The data can be useful for selecting the optimal conditions to obtain MSC and for further cryopreservation of umbilical cord tissue.

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Human umbilical cord-derived mesenchymal stem cells elicit macrophages into an anti-inflammatory phenotype to alleviate insulin resistance in type 2 diabetic rats

Stem Cells ◽

10.1002/stem.2238 ◽

2015 ◽

Vol 34 (3) ◽

pp. 627-639 ◽

Cited By ~ 63

Author(s):

Zongyan Xie ◽

Haojie Hao ◽

Chuan Tong ◽

Yu Cheng ◽

Jiejie Liu ◽

...

Keyword(s):

Insulin Resistance ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Diabetic Rats ◽

Human Umbilical Cord ◽

Inflammatory Phenotype ◽

Anti Inflammatory ◽

Type 2 Diabetic

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Clinical and imaging outcomes after intrathecal injection of umbilical cord tissue mesenchymal stem cells in cerebral palsy: a randomized double-blind sham-controlled clinical trial

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02513-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Man Amanat ◽

Anahita Majmaa ◽

Morteza Zarrabi ◽

Masoumeh Nouri ◽

Masood Ghahvechi Akbari ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cerebral Palsy ◽

Umbilical Cord ◽

Intrathecal Injection ◽

Control Group ◽

Umbilical Cord Tissue ◽

The Mean ◽

And Control ◽

Experimental Group

Abstract Background This study assessed the safety and efficacy of intrathecal injection of umbilical cord tissue mesenchymal stem cells (UCT-MSC) in individuals with cerebral palsy (CP). The diffusion tensor imaging (DTI) was performed to evaluate the alterations in white-matter integrity. Methods Participants (4–14 years old) with spastic CP were assigned in 1:1 ratio to receive either UCT-MSC or sham procedure. Single-dose (2 × 107) cells were administered in the experimental group. Small needle pricks to the lower back were performed in the sham-control arm. All individuals were sedated to prevent awareness. The primary endpoints were the mean changes in gross motor function measure (GMFM)-66 from baseline to 12 months after procedures. The mean changes in the modified Ashworth scale (MAS), pediatric evaluation of disability inventory (PEDI), and CP quality of life (CP-QoL) were also assessed. Secondary endpoints were the mean changes in fractional anisotropy (FA) and mean diffusivity (MD) of corticospinal tract (CST) and posterior thalamic radiation (PTR). Results There were 36 participants in each group. The mean GMFM-66 scores after 12 months of intervention were significantly higher in the UCT-MSC group compared to baseline (10.65; 95%CI 5.39, 15.91) and control (β 8.07; 95%CI 1.62, 14.52; Cohen’s d 0.92). The increase was also seen in total PEDI scores (vs baseline 8.53; 95%CI 4.98, 12.08; vs control: β 6.87; 95%CI 1.52, 12.21; Cohen’s d 0.70). The mean change in MAS scores after 12 months of cell injection reduced compared to baseline (−1.0; 95%CI −1.31, −0.69) and control (β −0.72; 95%CI −1.18, −0.26; Cohen’s d 0.76). Regarding CP-QoL, mean changes in domains including friends and family, participation in activities, and communication were higher than the control group with a large effect size. The DTI analysis in the experimental group showed that mean FA increased (CST 0.032; 95%CI 0.02, 0.03. PTR 0.024; 95%CI 0.020, 0.028) and MD decreased (CST −0.035 × 10-3; 95%CI −0.04 × 10-3, −0.02 × 10-3. PTR −0.045 × 10-3; 95%CI −0.05 × 10-3, −0.03 × 10-3); compared to baseline. The mean changes were significantly higher than the control group. Conclusions The UCT-MSC transplantation was safe and may improve the clinical and imaging outcomes. Trial registration The study was registered with ClinicalTrials.gov (NCT03795974).

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