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  1. Article ; Online: Neuronal-Hematopoietic Cell Fusion in Diabetic Neuropathy.

    Terashima, Tomoya / Katagi, Miwako / Ohashi, Natsuko

    Stem cells translational medicine

    2023  Volume 12, Issue 4, Page(s) 215–220

    Abstract: Diabetic neuropathy is a major complication of diabetes mellitus that occurs during the early stages of the disease. Many pathogenic mechanisms are related and induced by hyperglycemia. However, even if these factors improve, diabetic neuropathy cannot ... ...

    Abstract Diabetic neuropathy is a major complication of diabetes mellitus that occurs during the early stages of the disease. Many pathogenic mechanisms are related and induced by hyperglycemia. However, even if these factors improve, diabetic neuropathy cannot go into remission and progresses slowly. Furthermore, diabetic neuropathy often progresses even with proper glycemic control. Recently, bone marrow-derived cells (BMDCs) were reported to be involved in the pathogenesis of diabetic neuropathy. BMDCs expressing proinsulin and TNFα migrate to the dorsal root ganglion and fuse with neurons, and this neuronal-hematopoietic cell fusion induces neuronal dysfunction and apoptosis. The CD106-positive lineage-sca1+c-kit+ (LSK) stem cell fraction in the bone marrow is strongly involved in cell fusion with neurons, leading to diabetic neuropathy. Surprisingly, when CD106-positive LSK stem cells obtained from diabetic mice were transplanted into nondiabetic mice, they fused with dorsal root ganglion neurons and induced neuropathy in non-hyperglycemic normal mice. The transplanted CD106-positive LSK fraction inherited the trait even after transplantation; this "progeny effect" may explain the irreversibility of diabetic neuropathy and is a significant finding for determining the target of radical treatments and provides new directions for developing therapeutic methods for diabetic neuropathy.
    MeSH term(s) Mice ; Animals ; Bone Marrow Transplantation/adverse effects ; Diabetic Neuropathies/complications ; Diabetic Neuropathies/pathology ; Bone Marrow Cells ; Diabetes Mellitus, Experimental/complications ; Diabetes Mellitus, Experimental/pathology ; Cell Fusion ; Neurons/pathology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Mice, Inbred C57BL
    Language English
    Publishing date 2023-03-27
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2642270-0
    ISSN 2157-6580 ; 2157-6580
    ISSN (online) 2157-6580
    ISSN 2157-6580
    DOI 10.1093/stcltm/szad015
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Impaired circadian rhythm may disturb epithelialization in the wound healing of the skin in diabetic mice.

    Okano, Junko / Katagi, Miwako / Nakagawa, Takahiko / Kojima, Hideto

    Journal of dermatological science

    2023  Volume 110, Issue 1, Page(s) 31–34

    MeSH term(s) Mice ; Animals ; Diabetes Mellitus, Experimental ; Skin ; Wound Healing ; Re-Epithelialization
    Language English
    Publishing date 2023-03-21
    Publishing country Netherlands
    Document type Letter
    ZDB-ID 1024446-3
    ISSN 1873-569X ; 0923-1811
    ISSN (online) 1873-569X
    ISSN 0923-1811
    DOI 10.1016/j.jdermsci.2023.03.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Bone marrow-derived inducible microglia-like cells ameliorate motor function and survival in a mouse model of amyotrophic lateral sclerosis.

    Kobashi, Shuhei / Terashima, Tomoya / Katagi, Miwako / Urushitani, Makoto / Kojima, Hideto

    Cytotherapy

    2022  Volume 24, Issue 8, Page(s) 789–801

    Abstract: Background aims: Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease. Neuroinflammation in the spinal cord plays a pivotal role in the pathogenesis of ALS, and microglia are involved in neuroinflammation. Microglia mainly have ... ...

    Abstract Background aims: Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease. Neuroinflammation in the spinal cord plays a pivotal role in the pathogenesis of ALS, and microglia are involved in neuroinflammation. Microglia mainly have two opposite phenotypes involving cytotoxic and neuroprotective properties, and neuroprotective microglia are expected to be a novel application for the treatment of ALS. Therefore, to establish a clinically applicable therapeutic method using neuroprotective microglia, the authors investigated the effect of inducing neuroprotective microglia-like cells from bone marrow for transplantation into ALS model mice.
    Methods: Bone marrow-derived mononuclear cells were isolated from green fluorescent protein mice and cultured using different protocols of cytokine treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. Cells with a high potency of proliferation and differentiation into microglia were evaluated by gene analysis, flow cytometry and direct neuroprotective effects in vitro. These cells were named bone marrow-derived inducible microglia-like (BM-iMG) cells and transplanted into the spinal cords of ALS model mice, and behavioral tests, immunohistochemistry and gene expression profiling were performed.
    Results: Three-day GM-CSF and 4-day GM-CSF + IL-4 stimulations were most effective in inducing BM-iMG cells from the bone marrow. Transplantation of BM-iMG cells improved motor function, prolonged survival and suppressed neuronal cell death, astrogliosis and microgliosis in the spinal cords of ALS mice. Moreover, neuroprotective genes such as Arg1 and Mrc1 were upregulated, whereas pro-inflammatory genes such as Nos2 and Il6 were downregulated.
    Conclusions: Intraspinal transplantation of BM-iMG cells demonstrated therapeutic effects in a mouse model of ALS. Further studies and clinical applications in patients with ALS are expected in the future.
    MeSH term(s) Amyotrophic Lateral Sclerosis/therapy ; Animals ; Bone Marrow/metabolism ; Disease Models, Animal ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Interleukin-4/pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microglia/metabolism ; Neurodegenerative Diseases/therapy ; Spinal Cord/metabolism
    Chemical Substances Interleukin-4 (207137-56-2) ; Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1)
    Language English
    Publishing date 2022-04-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2039821-9
    ISSN 1477-2566 ; 1465-3249
    ISSN (online) 1477-2566
    ISSN 1465-3249
    DOI 10.1016/j.jcyt.2022.02.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Bone marrow-derived mononuclear cells ameliorate neurological function in chronic cerebral infarction model mice via improvement of cerebral blood flow.

    Kitamura, Tomoaki / Terashima, Tomoya / Katagi, Miwako / Ohashi, Natsuko / Nozaki, Kazuhiko / Tsuji, Atsushi

    Cytotherapy

    2023  Volume 25, Issue 11, Page(s) 1186–1199

    Abstract: Background aims: Stroke is a frequently observed neurological disorder that might lead to permanent and severe disability. Recently, various regenerative therapies have been developed, some of which have already been applied clinically. However, their ... ...

    Abstract Background aims: Stroke is a frequently observed neurological disorder that might lead to permanent and severe disability. Recently, various regenerative therapies have been developed, some of which have already been applied clinically. However, their outcomes have not been fully satisfactory. In particular, the development of regenerative therapies for chronic ischemic stroke is greatly needed. Herein intracerebral administration of bone marrow-derived mononuclear cells (BM-MNCs) was assessed as a potential treatment for chronic ischemic stroke using a severe combined immunodeficiency mouse model characterized by minimal vascular variation unrelated to immunodeficiency.
    Methods: A reproducible model of permanent middle cerebral artery occlusion was prepared, and intracerebral BM-MNC transplantation was performed 14 days after stroke induction in the infarcted brain.
    Results: Sensorimotor behavioral function and cerebral blood flow were significantly improved upon treatment with BM-MNCs compared to control medium injection. The transplanted cells exhibited characteristics of the vascular endothelium and microglia/macrophages. Significant angiogenesis and suppression of astrogliosis and microgliosis were observed in the affected brain. Messenger RNA expression analysis showed significant increases in anti-inflammatory cytokines, A2 astrocyte/anti-inflammatory microglia markers and vascular endothelial markers such as vascular endothelial growth factor and significant decreases in pro-inflammatory cytokines and A1 astrocyte/pro-inflammatory microglia markers following BM-MNC transplantation.
    Conclusions: These results suggest that intracerebral administration of BM-MNCs should be considered an effective cell therapy for chronic stroke.
    MeSH term(s) Mice ; Animals ; Vascular Endothelial Growth Factor A/genetics ; Bone Marrow ; Bone Marrow Cells/physiology ; Bone Marrow Transplantation/methods ; Stroke/therapy ; Brain Ischemia ; Ischemia ; Cytokines/analysis ; Infarction, Middle Cerebral Artery/therapy ; Ischemic Stroke ; Anti-Inflammatory Agents ; Cerebrovascular Circulation
    Chemical Substances Vascular Endothelial Growth Factor A ; Cytokines ; Anti-Inflammatory Agents
    Language English
    Publishing date 2023-08-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2039821-9
    ISSN 1477-2566 ; 1465-3249
    ISSN (online) 1477-2566
    ISSN 1465-3249
    DOI 10.1016/j.jcyt.2023.07.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Complete remission of diabetes with a transient HDAC inhibitor and insulin in streptozotocin mice.

    Kojima, Hideto / Katagi, Miwako / Okano, Junko / Nakae, Yuki / Ohashi, Natsuko / Fujino, Kazunori / Miyazawa, Itsuko / Nakagawa, Takahiko

    Communications biology

    2023  Volume 6, Issue 1, Page(s) 637

    Abstract: Despite the growing epidemic worldwide, diabetes is an incurable disease. We have been focusing on why diabetes manifests refractoriness to any therapy. We recently found that abnormal bone marrow-derived cells (BMDCs), namely, Vcam- ... ...

    Abstract Despite the growing epidemic worldwide, diabetes is an incurable disease. We have been focusing on why diabetes manifests refractoriness to any therapy. We recently found that abnormal bone marrow-derived cells (BMDCs), namely, Vcam-1
    MeSH term(s) Animals ; Mice ; Insulin ; Histone Deacetylase Inhibitors/pharmacology ; Histone Deacetylase Inhibitors/therapeutic use ; Streptozocin ; Diabetes Mellitus, Experimental ; Insulin, Regular, Human
    Chemical Substances Insulin ; givinostat (5P60F84FBH) ; Histone Deacetylase Inhibitors ; Streptozocin (5W494URQ81) ; Insulin, Regular, Human
    Language English
    Publishing date 2023-06-13
    Publishing country England
    Document type Journal Article
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-023-05010-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Aberrant bone marrow-derived microglia in the hypothalamus may dysregulate appetite in diabetes.

    Katagi, Miwako / Nakae, Yuki / Okano, Junko / Fujino, Kazunori / Tanaka, Tomoki / Miyazawa, Itsuko / Ohashi, Natsuko / Nakagawa, Takahiko / Kojima, Hideto

    Biochemical and biophysical research communications

    2023  Volume 682, Page(s) 132–137

    Abstract: Bone marrow derived cells (BMDCs) migrate into the hypothalamus, where those cells give rise to microglia to regulate food intake. Given the fact that diabetes functionally impairs BMDCs, we hypothesized that diabetic microglia would fail to exhibit ... ...

    Abstract Bone marrow derived cells (BMDCs) migrate into the hypothalamus, where those cells give rise to microglia to regulate food intake. Given the fact that diabetes functionally impairs BMDCs, we hypothesized that diabetic microglia would fail to exhibit physiological function, accounting for hyperphagia in diabetes. To examine the role of BMDCs, total bone marrow cells from GFP transgenic mice were transplanted into wild type mice in which diabetes was induced by streptozotocin. We first confirmed that bone marrow transplantation could be utilized to examine BMDCs in the brain parenchyma as GFP positive cells could engraft the brain parenchyma and give rise to microglia even when the BBB was intact in the recipient mice. While diabetic mice manifested hyperphagia, BMDCs were in smaller number in the hypothalamus with less response to fasting in the brain parenchyma compared to nondiabetic mice. This finding was also confirmed by examining nondiabetic chimera mice in which BMDCs were diabetic. Those mice also exhibited less response of BMDCs in response to fasting. In conclusion, diabetic BMDCs had less response of microglia to fasting, perhaps accounting for diabetic hyperphagia.
    MeSH term(s) Mice ; Animals ; Bone Marrow/metabolism ; Diabetes Mellitus, Experimental ; Microglia/metabolism ; Appetite ; Mice, Transgenic ; Bone Marrow Transplantation ; Bone Marrow Cells/metabolism ; Hyperphagia ; Hypothalamus/metabolism ; Mice, Inbred C57BL ; Green Fluorescent Proteins/metabolism
    Chemical Substances Green Fluorescent Proteins (147336-22-9)
    Language English
    Publishing date 2023-09-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2023.09.083
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  7. Article ; Online: Expression of proinflammatory cytokines and proinsulin by bone marrow-derived cells for fracture healing in long-term diabetic mice.

    Fujikawa, Hitomi / Kojima, Hideto / Terashima, Tomoya / Katagi, Miwako / Yayama, Takafumi / Kumagai, Kosuke / Mori, Kanji / Saito, Hideki / Imai, Shinji

    BMC musculoskeletal disorders

    2023  Volume 24, Issue 1, Page(s) 585

    Abstract: Background: Diabetes mellitus (DM) causes bone dysfunction due to poor bone quality, leading to severe deterioration in patient of quality of life. The mechanisms of bone metabolism in DM remain unclear, although chemical and/or mechanical factors are ... ...

    Abstract Background: Diabetes mellitus (DM) causes bone dysfunction due to poor bone quality, leading to severe deterioration in patient of quality of life. The mechanisms of bone metabolism in DM remain unclear, although chemical and/or mechanical factors are known to disrupt the homeostasis of osteoblasts and osteoclasts. The purpose of this study was to identify the changes of osteoblasts and osteoclasts under long-term hyperglycaemic conditions, using a mouse fracture model of long-term hyperglycemia (LT-HG).
    Methods: C57BL/6J mice and green fluorescent protein (GFP) -positive bone marrow transplanted C57BL/6J mice with LT-HG, maintained under a state of hyperglycaemia for 2 months, were used in this study. After the experimental fracture, we examined the immunohistochemical expression of proinsulin and tumor necrosis factor (TNF) -α at the fracture site. C57BL/6J fracture model mice without hyperglycaemia were used as controls.
    Results: In the LT-HG mice, chondrocyte resorption was delayed, and osteoblasts showed an irregular arrangement at the callus site. The osteoclasts were scattered with a decrement in the number of nuclei. The expression of proinsulin was confirmed in bone marrow derived cells (BMDCs) with neovascularization 2 and 3 weeks after fracture. Immunopositivity for TNF-α was also confirmed in immature chondrocytes and BMDCs with neovascularization at 2 weeks, and the number of positive cells was not decreased at 3 weeks. Examination of GFP-grafted hyperglycaemic mice showed that the majority of cells at the fracture site were GFP-positive. Immunohistochemistry showed that the rate of double positives was 15% for GFP and proinsulin and 47% for GFP and TNF-α.
    Conclusion: LT-HG induces an increase in the number of proinsulin and TNF-α positive cells derived from BMDCs. We suggest that proinsulin and TNF-α positive cells are involved in both bone formation and bone resorption after fracture under hyperglycaemic conditions, resulting in the delay of bone healing.
    MeSH term(s) Animals ; Mice ; Fracture Healing ; Cytokines ; Tumor Necrosis Factor-alpha/metabolism ; Proinsulin ; Bone Marrow/pathology ; Diabetes Mellitus, Experimental/complications ; Quality of Life ; Mice, Inbred C57BL ; Bony Callus/pathology ; Fractures, Bone/pathology ; Hyperglycemia/complications ; Hyperglycemia/pathology ; Bone Marrow Cells/metabolism
    Chemical Substances Cytokines ; Tumor Necrosis Factor-alpha ; Proinsulin (9035-68-1)
    Language English
    Publishing date 2023-07-18
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041355-5
    ISSN 1471-2474 ; 1471-2474
    ISSN (online) 1471-2474
    ISSN 1471-2474
    DOI 10.1186/s12891-023-06710-5
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  8. Article ; Online: GLT1 gene delivery based on bone marrow-derived cells ameliorates motor function and survival in a mouse model of ALS.

    Ohashi, Natsuko / Terashima, Tomoya / Katagi, Miwako / Nakae, Yuki / Okano, Junko / Suzuki, Yoshihisa / Kojima, Hideto

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 12803

    Abstract: Amyotrophic lateral sclerosis (ALS) is an intractable neurodegenerative disease. CD68-positive bone marrow (BM)-derived cells (BMDCs) accumulate in the pathological lesion in the SOD1(G93A) ALS mouse model after BM transplantation (BMT). Therefore, we ... ...

    Abstract Amyotrophic lateral sclerosis (ALS) is an intractable neurodegenerative disease. CD68-positive bone marrow (BM)-derived cells (BMDCs) accumulate in the pathological lesion in the SOD1(G93A) ALS mouse model after BM transplantation (BMT). Therefore, we investigated whether BMDCs can be applied as gene carriers for cell-based gene therapy by employing the accumulation of BMDCs. In ALS mice, YFP reporter signals were observed in 12-14% of white blood cells (WBCs) and in the spinal cord via transplantation of BM after lentiviral vector (LV) infection. After confirmation of gene transduction by LV with the CD68 promoter in 4-7% of WBCs and in the spinal cord of ALS mice, BM cells were infected with LVs expressing glutamate transporter (GLT) 1 that protects neurons from glutamate toxicity, driven by the CD68 promoter, which were transplanted into ALS mice. The treated mice showed improvement of motor behaviors and prolonged survival. Additionally, interleukin (IL)-1β was significantly suppressed, and IL-4, arginase 1, and FIZZ were significantly increased in the mice. These results suggested that GLT1 expression by BMDCs improved the spinal cord environment. Therefore, our gene therapy strategy may be applied to treat neurodegenerative diseases such as ALS in which BMDCs accumulate in the pathological lesion by BMT.
    MeSH term(s) Amyotrophic Lateral Sclerosis/complications ; Amyotrophic Lateral Sclerosis/physiopathology ; Animals ; Biomarkers/metabolism ; Bone Marrow Cells/metabolism ; Bone Marrow Transplantation ; Cell Survival ; Cytokines/genetics ; Cytokines/metabolism ; Disease Models, Animal ; Disease Progression ; Excitatory Amino Acid Transporter 2/genetics ; Gene Expression Regulation ; Gene Transfer Techniques ; Genetic Therapy ; Gliosis/complications ; Gliosis/pathology ; Gliosis/physiopathology ; Glutamic Acid/metabolism ; Lentivirus/metabolism ; Mice, Inbred C57BL ; Mice, Transgenic ; Microglia/metabolism ; Motor Activity/physiology ; Motor Neurons/metabolism ; Muscular Atrophy/complications ; Muscular Atrophy/pathology ; Muscular Atrophy/physiopathology ; Nerve Degeneration/complications ; Nerve Degeneration/pathology ; Nerve Degeneration/physiopathology ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Spinal Cord/metabolism ; Superoxide Dismutase-1/metabolism ; Survival Analysis ; Mice
    Chemical Substances Biomarkers ; Cytokines ; Excitatory Amino Acid Transporter 2 ; RNA, Messenger ; Slc1a2 protein, mouse ; Glutamic Acid (3KX376GY7L) ; Superoxide Dismutase-1 (EC 1.15.1.1)
    Language English
    Publishing date 2021-06-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-92285-x
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  9. Article: Ambient Temperature Is Correlated With the Severity of Neonatal Hypoxic-Ischemic Brain Injury via Microglial Accumulation in Mice.

    Zen, Rika / Terashima, Tomoya / Tsuji, Shunichiro / Katagi, Miwako / Ohashi, Natsuko / Nobuta, Yuri / Higuchi, Asuka / Kanai, Hirohiko / Murakami, Takashi / Kojima, Hideto

    Frontiers in pediatrics

    2022  Volume 10, Page(s) 883556

    Abstract: Background: The pathophysiology of neonatal hypoxic-ischemic encephalopathy (HIE) has been studied in several rodent models to develop novel treatments. Although it is well known that high ambient temperature results in severe HIE, the effect of subtle ... ...

    Abstract Background: The pathophysiology of neonatal hypoxic-ischemic encephalopathy (HIE) has been studied in several rodent models to develop novel treatments. Although it is well known that high ambient temperature results in severe HIE, the effect of subtle changes in ambient temperature during a hypoxic-ischemic (HI) insult has not been studied. Therefore, in order to clarify the difference of pathophysiological change among the HIE models due to the influence of small changes in chamber temperature, three-step gradual change of 0.5°C each were prepared in ambient temperature during hypoxic exposure.
    Methods: Blood flow in the left common carotid artery (CCA) of neonatal mice was interrupted using bipolar electronic forceps under general and local anesthesia. The mice were subsequently subjected to 10% hypoxic exposure for 50 min at 36.0, 36.5, or 37.0°C. A control group was also included in the study. The size of the striatum and hippocampus and the volume reduction rate of the hemisphere in the section containing them on the ischemic side were evaluated using microtubule associated protein 2 (MAP2) immunostaining. The accumulation of Iba1-positive cells was investigated to assess inflammation. Additionally, rotarod and open-field tests were performed 2 weeks after HI insult to assess its effect on physiological conditions.
    Results: MAP2 staining revealed that the higher the temperature during hypoxia, the more severe the volume reduction rate in the hemisphere, striatum, and hippocampus. The number of Iba1-positive cells in the ipsilateral lesion gradually increased with increasing temperature, and there was a significant difference in motor function in the 36.5 and 37.0°C groups compared with the sham group. In the open-field tests, there was a significant decrease in performance in the 37.0°C groups compared with the 36.0°C and sham groups.
    Conclusions: Even a small gradual change of 0.5°C produced a significant difference in pathological and behavioral changes and contributed to the accumulation of Iba1-positive cells. The arrangement of ambient temperature is useful for creating a rodent model with the appropriate severity of the targeted neuropsychological symptoms to establish a novel therapy for HIE.
    Language English
    Publishing date 2022-05-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2711999-3
    ISSN 2296-2360
    ISSN 2296-2360
    DOI 10.3389/fped.2022.883556
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  10. Article ; Online: Bone marrow-derived vasculogenesis leads to scarless regeneration in deep wounds with periosteal defects.

    Shirai, Yuuki / Okano, Junko / Nakagawa, Takahiko / Katagi, Miwako / Nakae, Yuki / Arakawa, Atsuhiro / Koshinuma, Shinya / Yamamoto, Gaku / Kojima, Hideto

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 20589

    Abstract: Deep skin wounds with periosteal defects, frequently caused by traffic accidents or radical dissection, are refractory. Transplant surgery is frequently performed, but patients are subjected to stress for long operation periods, the sacrifice of donor ... ...

    Abstract Deep skin wounds with periosteal defects, frequently caused by traffic accidents or radical dissection, are refractory. Transplant surgery is frequently performed, but patients are subjected to stress for long operation periods, the sacrifice of donor regions, or several complications, such as flap necrosis or intractable ulcers. Even if the defects are covered, a scar composed of fibrous tissue remains in the body, which can cause itching, dysesthesia, or repeated ulcers because of the lack of distribution of peripheral nerves or hair follicles. Thus, treatments with the aim of regenerating lost tissue for deep wounds with periosteal defects are needed. Here, we show that the use of gelatin sponges (GS), which have been used as haemostatic materials in clinical practice, allowed the regeneration of heterogeneous tissues, including periosteum, skin, and skin appendages, when used as scaffolds in deep wounds with periosteal defects in rats. Bone marrow transplantation in rats revealed the mechanism by which the microenvironment provided by GS enabled bone marrow-derived cells (BMDCs) to form a vascular niche, followed by regeneration of the periosteum, skin, or skin appendages such as hair follicles by local cells. Our findings demonstrated that vascular niche formation provided by BMDCs is crucial for heterogeneous tissue regeneration.
    MeSH term(s) Animals ; Rats ; Bone Marrow ; Ulcer ; Hair Follicle ; Skin ; Periosteum ; Gelatin
    Chemical Substances Gelatin (9000-70-8)
    Language English
    Publishing date 2022-11-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-24957-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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