The Therapeutic Potential of Conditioned Medium from Human Breast Milk Stem Cells in Treating Spinal Cord Injury

Borhani-Haghighi, Maryam; Navid, Shadan; Mohamadi, Yousef

doi:10.31616/asj.2019.0026

Cited by 16 publications

(5 citation statements)

References 29 publications

(34 reference statements)

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“…In this study, after administering HNSCs-secretome to SCI-affected rats, there was a decrease in the pro-inflammatory cytokine TNF-α, accordance with five previous studies by Huang et al [ 23 ], Cizkova et al [ 24 ], Huang et al [ 25 ], and Borhani-Haghighi et al [ 26 ], who stated that there was a decrease in TNF-α after MSC-secretome intervention in mouse-model SCI. The cytokine TNF-α is the most influential proinflammatory mediator in SCI, followed by other proinflammatory mediators such as interferon gamma, IL-6, and IL-8[ 27 ].…”

Section: Discussionsupporting

confidence: 91%

Mechanism of spinal cord injury regeneration and the effect of human neural stem cells-secretome treatment in rat model

Semita¹,

Utomo²,

Suroto³

2023

World J Orthop

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BACKGROUND Globally, complete neurological recovery of spinal cord injury (SCI) is still less than 1%, and 90% experience permanent disability. The key issue is that a pharmacological neuroprotective-neuroregenerative agent and SCI regeneration mechanism have not been found. The secretomes of stem cell are an emerging neurotrophic agent, but the effect of human neural stem cells (HNSCs) secretome on SCI is still unclear. AIM To investigate the regeneration mechanism of SCI and neuroprotective-neuroregenerative effects of HNSCs-secretome on subacute SCI post-laminectomy in rats. METHODS An experimental study was conducted with 45 Rattus norvegicus, divided into 15 normal, 15 control (10 mL physiologic saline), and 15 treatment (30 μL HNSCs-secretome, intrathecal T10, three days post-traumatic). Locomotor function was evaluated weekly by blinded evaluators. Fifty-six days post-injury, specimens were collected, and spinal cord lesion, free radical oxidative stress (F2-Isoprostanes), nuclear factor-kappa B (NF-κB), matrix metallopeptidase 9 (MMP9), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), transforming growth factor-beta (TGF-β), vascular endothelial growth factor (VEGF), B cell lymphoma-2 (Bcl-2), nestin, brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) were analyzed. The SCI regeneration mechanism was analyzed using partial least squares structural equation modeling (PLS SEM). RESULTS HNSCs-secretome significantly improved locomotor recovery according to Basso, Beattie, Bresnahan (BBB) scores and increased neurogenesis (nestin, BDNF, and GDNF), neuroangiogenesis (VEGF), anti-apoptotic (Bcl-2), anti-inflammatory (IL-10 and TGF-β), but decreased pro-inflammatory (NF-κB, MMP9, TNF-α), F2-Isoprostanes, and spinal cord lesion size. The SCI regeneration mechanism is valid by analyzed outer model, inner model, and hypothesis testing in PLS SEM, started with pro-inflammation followed by anti-inflammation, anti-apoptotic, neuroangiogenesis, neurogenesis, and locomotor function. CONCLUSION HNSCs-secretome as a potential neuroprotective-neuroregenerative agent for the treatment of SCI and uncover the SCI regeneration mechanism.

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Section: Discussionsupporting

confidence: 91%

Mechanism of spinal cord injury regeneration and the effect of human neural stem cells-secretome treatment in rat model

Semita¹,

Utomo²,

Suroto³

2023

World J Orthop

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“…To assess the locomotor expression, the BBB open-field test was performed on days 1, 3, 7, 14, 21, and 28 after injury [ 16 ]. The BBB measures the tail, body, legs, trunk stability, limb movement, and toe clearance, all of which are examined to measure the locomotor abilities [ 20 , 21 ]. The score shows a range of numbers between 0 and 21.…”

Section: Methodsmentioning

confidence: 99%

The mechanism of human neural stem cell secretomes improves neuropathic pain and locomotor function in spinal cord injury rat models: through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities

et al. 2022

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Background: Globally, spinal cord injury (SCI) results in a big burden, including 90% suffering permanent disability, and 60%-69% experiencing neuropathic pain. The main causes are oxidative stress, inflammation, and degeneration. The efficacy of the stem cell secretome is promising, but the role of human neural stem cell (HNSC)secretome in neuropathic pain is unclear. This study evaluated how the mechanism of HNSC-secretome improves neuropathic pain and locomotor function in SCI rat models through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities. Methods: A proper experimental study investigated 15 Rattus norvegicus divided into normal, control, and treatment groups (30 µL HNSC-secretome, intrathecal in the level of T10, three days post-traumatic SCI). Twentyeight days post-injury, specimens were collected, and matrix metalloproteinase (MMP)-9, F2-Isoprostanes, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and brain derived neurotrophic factor (BDNF) were analyzed. Locomotor recovery was evaluated via Basso, Beattie, and Bresnahan scores. Neuropathic pain was evaluated using the Rat Grimace Scale. Results: The HNSC-secretome could improve locomotor recovery and neuropathic pain, decrease F2-Isoprostane (antioxidant), decrease MMP-9 and TNF-α (anti-inflammatory), as well as modulate TGF-β and BDNF (neurotrophic factor). Moreover, HNSC-secretomes maintain the extracellular matrix of SCI by reducing the matrix degradation effect of MMP-9 and increasing the collagen formation effect of TGF-β as a resistor of glial scar formation. Conclusions: The present study demonstrated the mechanism of HNSC-secretome in improving neuropathic pain and locomotor function in SCI through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities.

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“…However, further research is required to prove this hypothesis. A recent study using breast milk stem cells to treat spinal cord injury showed that the administration of these cells reduced apoptosis and inflammation at the site of injury, indicating their influence on immune responses and therapeutic potential ( 258 ).…”

Section: The Importance Of Breast Milk For the Development Of The Neonatementioning

confidence: 99%

Maternal Microbiota, Early Life Colonization and Breast Milk Drive Immune Development in the Newborn

et al. 2021

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The innate immune system is the oldest protection strategy that is conserved across all organisms. Although having an unspecific action, it is the first and fastest defense mechanism against pathogens. Development of predominantly the adaptive immune system takes place after birth. However, some key components of the innate immune system evolve during the prenatal period of life, which endows the newborn with the ability to mount an immune response against pathogenic invaders directly after birth. Undoubtedly, the crosstalk between maternal immune cells, antibodies, dietary antigens, and microbial metabolites originating from the maternal microbiota are the key players in preparing the neonate’s immunity to the outer world. Birth represents the biggest substantial environmental change in life, where the newborn leaves the protective amniotic sac and is exposed for the first time to a countless variety of microbes. Colonization of all body surfaces commences, including skin, lung, and gastrointestinal tract, leading to the establishment of the commensal microbiota and the maturation of the newborn immune system, and hence lifelong health. Pregnancy, birth, and the consumption of breast milk shape the immune development in coordination with maternal and newborn microbiota. Discrepancies in these fine-tuned microbiota interactions during each developmental stage can have long-term effects on disease susceptibility, such as metabolic syndrome, childhood asthma, or autoimmune type 1 diabetes. In this review, we will give an overview of the recent studies by discussing the multifaceted emergence of the newborn innate immune development in line with the importance of maternal and early life microbiota exposure and breast milk intake.

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The Therapeutic Potential of Conditioned Medium from Human Breast Milk Stem Cells in Treating Spinal Cord Injury

Cited by 16 publications

References 29 publications

Mechanism of spinal cord injury regeneration and the effect of human neural stem cells-secretome treatment in rat model

Mechanism of spinal cord injury regeneration and the effect of human neural stem cells-secretome treatment in rat model

The mechanism of human neural stem cell secretomes improves neuropathic pain and locomotor function in spinal cord injury rat models: through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities

Maternal Microbiota, Early Life Colonization and Breast Milk Drive Immune Development in the Newborn

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