Human amniotic fluid stem cells have a unique potential to accelerate cutaneous wound healing with reduced fibrotic scarring like a fetus

Fukutake, Marie; Ochiai, Daigo; Masuda, H.; Abe, Yushi; Sato, Yu; Otani, Toshiro; Sakai, Shigeki; Aramaki-Hattori, Noriko; Shimoda, Masayuki; Matsumoto, Tadashi; Miyakoshi, Kei; Kanai, Yae; Kishi, Kazuo; Tanaka, Mamoru

doi:10.1007/s13577-018-0222-1

Cited by 33 publications

(35 citation statements)

References 46 publications

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“…S2A). In accordance with our previous studies [18,20], spindle-shaped CD117 + cells (i.e., hAFSCs) were expanded (Supporting Information Fig. S2B).…”

Section: Isolation and Characterization Of Hafscssupporting

confidence: 89%

“…In this study, we clearly demonstrated that hAFSCs can cover the MMC defect and that some hAFSCs directly differentiate into cytokeratin-expressing cells, a main component of the skin epidermis. Previously, we and other groups reported that hAFSCs themselves and their secretomes can accelerate wound closure by enhancing reepithelialization using a dorsal excisional cutaneous wound model in BALB/c mice [20,32,33]. Furthermore, hAFSCs promote cutaneous wound closure through the direct differentiation into keratinocytes in vivo and have the potential to differentiate into epidermal-lineage cells including keratinocytes of various maturity levels in vitro [32].…”

Section: Discussionmentioning

confidence: 93%

“…Quantitative polymerase chain reaction (PCR) was performed in duplicate in a volume of 25 μl per reaction using a 96‐well Bio‐Rad CFX96 Real‐Time PCR System (Bio‐Rad, Richmond, CA). Reaction mixtures included 5 ng of genomic DNA as the template, 0.4 mM of each primer (Thermo Fisher Scientific, Waltham, MA), SYBR Premix Ex Taq II (Tli RNaseH Plus; Takara Bio), and sterile H 2 O . The primer sets are listed in Supporting Information Table S3.…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, to determine the expression of trophic factors derived from hAFSCs in rat amniotic fluid, we isolated CD117 + amniotic fluid cells from E19and E21-rat amniotic fluid cells using CD117 MicroBeads (Miltenyi Biotec). [18,20]. The primer sets are listed in Supporting Information Table S3.…”

Section: Analysis Of E21-rat Amniotic Fluid Cellsmentioning

confidence: 99%

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In Utero Amniotic Fluid Stem Cell Therapy Protects Against Myelomeningocele via Spinal Cord Coverage and Hepatocyte Growth Factor Secretion

Abe

Ochiai

Masuda

et al. 2019

Stem Cells Translational Medicine

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Despite the poor prognosis associated with myelomeningocele (MMC), the options for prenatal treatments are still limited. Recently, fetal cellular therapy has become a new option for treating birth defects, although the therapeutic effects and mechanisms associated with such treatments remain unclear. The use of human amniotic fluid stem cells (hAFSCs) is ideal with respect to immunoreactivity and cell propagation. The prenatal diagnosis of MMC during early stages of pregnancy could allow for the ex vivo proliferation and modulation of autologous hAFSCs for use in utero stem cell therapy. Therefore, we investigated the therapeutic effects and mechanisms of hAFSCs‐based treatment for fetal MMC. hAFSCs were isolated as CD117‐positive cells from the amniotic fluid of 15‐ to 17‐week pregnant women who underwent amniocentesis for prenatal diagnosis and consented to this study. Rat dams were exposed to retinoic acid to induce fetal MMC and were subsequently injected with hAFSCs in each amniotic cavity. We measured the exposed area of the spinal cord and hepatocyte growth factor (HGF) levels at the lesion. The exposed spinal area of the hAFSC‐treated group was significantly smaller than that of the control group. Immunohistochemical analysis demonstrated a reduction in neuronal damage such as neurodegeneration and astrogliosis in the hAFSC‐treated group. Additionally, in lesions of the hAFSC‐treated group, HGF expression was upregulated and HGF‐positive hAFSCs were identified, suggesting that these cells migrated to the lesion and secreted HGF to suppress neuronal damage and induce neurogenesis. Therefore, in utero hAFSC therapy could become a novel strategy for fetal MMC. Stem Cells Translational Medicine 2019;8:1170–1179

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“…S2A). In accordance with our previous studies [18,20], spindle-shaped CD117 + cells (i.e., hAFSCs) were expanded (Supporting Information Fig. S2B).…”

Section: Isolation and Characterization Of Hafscssupporting

confidence: 89%

Section: Discussionmentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Analysis Of E21-rat Amniotic Fluid Cellsmentioning

confidence: 99%

See 2 more Smart Citations

In Utero Amniotic Fluid Stem Cell Therapy Protects Against Myelomeningocele via Spinal Cord Coverage and Hepatocyte Growth Factor Secretion

Abe

Ochiai

Masuda

et al. 2019

Stem Cells Translational Medicine

Self Cite

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“…With ascending evidence in the eld of the validity of stem cell supernatant in remission of scarring [28,29], there is a good rationale for pursuing the development of ADSCC-CM as new potential therapeutic agents. Notably, α-SMA and collagen deposition related to the activity of the TGF-β/Smad2 signalling pathway participates in the transition of broblasts/myo broblasts [30]. In light of this potential to affect the pathophysiological processes in HS development, the alleviation of α-SMA expression also illustrates a suppressive role in scarring.…”

Section: Discussionmentioning

confidence: 99%

Combination of Lyophilized Adipose-Derived Stem Cells Concentrated Conditioned Medium and Polysaccharide Hydrogel in the Inhibition of Hypertrophic Scarring

Zhang

Wang

Zhang

et al. 2020

Preprint

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BackgroundMesenchymal stem cell-based acellular therapies have been widely exploited in managing hypertrophic scar. However, low maintenance dose and transitory therapeutic effects during topical medication remain a thorny issue. Herein, this study aimed to optimize the curative effect of adipose-derived stem cells conditioned medium (ADSC-CM) in the prevention of hypertrophic scarring. MethodsIn the present study, ADSC-CM was concentrated via the freeze-drying procedure. The efficacy of different dose groups (CM, CM5, CM10) was conducted on the proliferation, apoptosis, and α-smooth muscle actin (α-SMA) expression of human keloid fibroblasts (HKFs) in vitro. Incorporation of adipose-derived stem cells concentrated conditioned medium (ADSCC-CM) into polysaccharide hydrogel was investigated in rabbit ear, in vivo. Haematoxylin-eosin (H&E) and Masson's trichrome staining were performed for the evaluation of scar hyperplasia. ResultsWe noted that ADSCC-CM could downregulate the α-SMA expression of HKFs in a dose-dependent manner. In the rabbit ear model, the scar hyperplasia in the medium-dose group (CM5) and high-dose group (CM10) was inhibited with reduced scar elevation index (SEI) under 4 months of observation. It is noteworthy that the union of CM5 and polysaccharide hydrogel (CM5+H) yielded the best preventive effect on scar hyperplasia. Briefly, melanin, height, vascularity and pliability in the CM5+H group were better than those of the control group. Collagen was evenly distributed, and skin appendages could be regenerated.ConclusionsAltogether, ADSCC-CM can downregulate the expression of α-SMA due to its anti-fibrosis effect, and promote the rearrangement of collagen fibres, which is integral to scar precaution. The in situ cross bonding of ADSCC-CM and polysaccharide hydrogel could remarkably enhance the therapeutic outcomes in inhibiting scar proliferation. Hence, the alliance of ADSCC-CM and hydrogel may become a potential alternative in hypertrophic scar prophylaxis.

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Sustained release of sulforaphane by bioactive extracellular vesicles for neuroprotective effect on chick model

2022

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Novel studies have shown neurological treatment possibilities with extracellular vesicles (EVs) as natural particles with a special composition that are produced by different cell types. Their stability, natural structure, composition, and bioavailability make them good candidates as drug vehicles. Here, EVs were isolated from amniotic fluid (AF) through differential centrifugation, and characterized for size (<200 nm), structure, and composition, their effectiveness on the human PC12 cell line, and brain of chick embryos exposed to sodium valproate (animal autistic model). Sulforaphane (SFN) was employed as a bioactive compound and then encapsulated into Evs using three methods including passive (incubation), active (sonication), and active‐passive (sonication‐incubation). Further, the loading and in vitro releases of SFN fitted the Korsmeyer–Peppas (R2 = 0.99) kinetic model by non‐Fickian diffusion case II (n = 0.44, passive loading) and Fickian diffusion case I (n = 0.41, active and active‐passive loading). SFN‐loaded EVs (SFN@EVs; 11 μM: 103 nM) stimulated hPC‐12 cell proliferation. The gene expression analysis revealed that SFN@EVs could upregulate Nrf2 and reduce IL‐6 expression. Eventually, histopathological results of the coronal cross‐section of the chick embryos brain showed treatment with SFN@EVs. This treatment illustrated normality in the gray and white matter and the orientation of the bipolar neurons. Our findings showed EVs' potentially acting as a gene expression regulator in autism spectrum disorder.

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Human amniotic fluid stem cells have a unique potential to accelerate cutaneous wound healing with reduced fibrotic scarring like a fetus

Cited by 33 publications

References 46 publications

In Utero Amniotic Fluid Stem Cell Therapy Protects Against Myelomeningocele via Spinal Cord Coverage and Hepatocyte Growth Factor Secretion

In Utero Amniotic Fluid Stem Cell Therapy Protects Against Myelomeningocele via Spinal Cord Coverage and Hepatocyte Growth Factor Secretion

Combination of Lyophilized Adipose-Derived Stem Cells Concentrated Conditioned Medium and Polysaccharide Hydrogel in the Inhibition of Hypertrophic Scarring

Sustained release of sulforaphane by bioactive extracellular vesicles for neuroprotective effect on chick model

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