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Article: Xenotransplantation and interspecies organogenesis: current status and issues.

Kano, Mayuko / Mizutani, Eiji / Homma, Shota / Masaki, Hideki / Nakauchi, Hiromitsu

2022 Volume 13, Page(s) 963282

Abstract: Pancreas (and islet) transplantation is the only curative treatment for type 1 diabetes patients whose β-cell functions have been abolished. However, the lack of donor organs has been the major hurdle to save a large number of patients. Therefore, ... ...

Abstract	Pancreas (and islet) transplantation is the only curative treatment for type 1 diabetes patients whose β-cell functions have been abolished. However, the lack of donor organs has been the major hurdle to save a large number of patients. Therefore, transplantation of animal organs is expected to be an alternative method to solve the serious shortage of donor organs. More recently, a method to generate organs from pluripotent stem cells inside the body of other species has been developed. This interspecies organ generation using blastocyst complementation (BC) is expected to be the next-generation regenerative medicine. Here, we describe the recent advances and future prospects for these two approaches.
MeSH term(s)	Animals ; Blastocyst ; Organogenesis/physiology ; Pluripotent Stem Cells ; Regenerative Medicine ; Transplantation, Heterologous
Language	English
Publishing date	2022-08-05
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2022.963282
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Article ; Online: Interspecies chimeras for human stem cell research.

Masaki, Hideki / Nakauchi, Hiromitsu

Development (Cambridge, England)

2017 Volume 144, Issue 14, Page(s) 2544–2547

Abstract: Interspecies chimeric assays are a valuable tool for investigating the potential of human stem and progenitor cells, as well as their differentiated progeny. This Spotlight article discusses the different factors that affect interspecies chimera ... ...

Abstract	Interspecies chimeric assays are a valuable tool for investigating the potential of human stem and progenitor cells, as well as their differentiated progeny. This Spotlight article discusses the different factors that affect interspecies chimera generation, such as evolutionary distance, developmental timing, and apoptosis of the transplanted cells, and suggests some possible strategies to address them. A refined approach to generating interspecies chimeras could contribute not only to a better understanding of cellular potential, but also to understanding the nature of xenogeneic barriers and mechanisms of heterochronicity, to modeling human development, and to the creation of human transplantable organs.
MeSH term(s)	Animals ; Apoptosis ; Embryonic Development ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/transplantation ; Humans ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/transplantation ; Species Specificity ; Stem Cell Research/ethics ; Transplantation Chimera
Language	English
Publishing date	2017--15
Publishing country	England
Document type	Journal Article
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.151183
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Article ; Online: Skin graft with dermis and appendages generated in vivo by cell competition.

Nagano, Hisato / Mizuno, Naoaki / Sato, Hideyuki / Mizutani, Eiji / Yanagida, Ayaka / Kano, Mayuko / Kasai, Mariko / Yamamoto, Hiromi / Watanabe, Motoo / Suchy, Fabian / Masaki, Hideki / Nakauchi, Hiromitsu

Nature communications

2024 Volume 15, Issue 1, Page(s) 3366

Abstract: Autologous skin grafting is a standard treatment for skin defects such as burns. No artificial skin substitutes are functionally equivalent to autologous skin grafts. The cultured epidermis lacks the dermis and does not engraft deep wounds. Although ... ...

Abstract	Autologous skin grafting is a standard treatment for skin defects such as burns. No artificial skin substitutes are functionally equivalent to autologous skin grafts. The cultured epidermis lacks the dermis and does not engraft deep wounds. Although reconstituted skin, which consists of cultured epidermal cells on a synthetic dermal substitute, can engraft deep wounds, it requires the wound bed to be well-vascularized and lacks skin appendages. In this study, we successfully generate complete skin grafts with pluripotent stem cell-derived epidermis with appendages on p63 knockout embryos' dermis. Donor pluripotent stem cell-derived keratinocytes encroach the embryos' dermis by eliminating p63 knockout keratinocytes based on cell-extracellular matrix adhesion mediated cell competition. Although the chimeric skin contains allogenic dermis, it is engraftable as long as autologous grafts. Furthermore, we could generate semi-humanized skin segments by human keratinocytes injection into the amnionic cavity of p63 knockout mice embryos. Niche encroachment opens the possibility of human skin graft production in livestock animals.
MeSH term(s)	Animals ; Skin Transplantation/methods ; Keratinocytes/cytology ; Keratinocytes/transplantation ; Humans ; Dermis/cytology ; Dermis/transplantation ; Mice, Knockout ; Mice ; Epidermis/metabolism ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/transplantation ; Skin, Artificial ; Epidermal Cells/transplantation ; Epidermal Cells/cytology ; Extracellular Matrix/metabolism ; Skin/cytology
Language	English
Publishing date	2024-04-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-47527-7
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Article ; Online: Publisher Correction: Hypoblast from human pluripotent stem cells regulates epiblast development.

Okubo, Takumi / Rivron, Nicolas / Kabata, Mio / Masaki, Hideki / Kishimoto, Keiko / Semi, Katsunori / Nakajima-Koyama, May / Kunitomi, Haruko / Kaswandy, Belinda / Sato, Hideyuki / Nakauchi, Hiromitsu / Woltjen, Knut / Saitou, Mitinori / Sasaki, Erika / Yamamoto, Takuya / Takashima, Yasuhiro

Nature

2024 Volume 626, Issue 8001, Page(s) E21

Language	English
Publishing date	2024-02-10
Publishing country	England
Document type	Published Erratum
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-024-07166-w
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Article ; Online: Functional calcium-responsive parathyroid glands generated using single-step blastocyst complementation.

Kano, Mayuko / Mizuno, Naoaki / Sato, Hideyuki / Kimura, Takaharu / Hirochika, Rei / Iwasaki, Yasumasa / Inoshita, Naoko / Nagano, Hisato / Kasai, Mariko / Yamamoto, Hiromi / Yamaguchi, Tomoyuki / Suga, Hidetaka / Masaki, Hideki / Mizutani, Eiji / Nakauchi, Hiromitsu

Proceedings of the National Academy of Sciences of the United States of America

2023 Volume 120, Issue 28, Page(s) e2216564120

Abstract: Patients with permanent hypoparathyroidism require lifelong replacement therapy to avoid life-threatening complications, The benefits of conventional treatment are limited, however. Transplanting a functional parathyroid gland (PTG) would yield better ... ...

Abstract	Patients with permanent hypoparathyroidism require lifelong replacement therapy to avoid life-threatening complications, The benefits of conventional treatment are limited, however. Transplanting a functional parathyroid gland (PTG) would yield better results. Parathyroid gland cells generated from pluripotent stem cells in vitro to date cannot mimic the physiological responses to extracellular calcium that are essential for calcium homeostasis. We thus hypothesized that blastocyst complementation (BC) could be a better strategy for generating functional PTG cells and compensating loss of parathyroid function. We here describe generation of fully functional PTGs from mouse embryonic stem cells (mESCs) with single-step BC. Using CRISPR-Cas9 knockout of
MeSH term(s)	Humans ; Animals ; Mice ; Rats ; Parathyroid Glands ; Calcium ; Hypoparathyroidism/genetics ; Hypoparathyroidism/therapy ; Calcium, Dietary ; Blastocyst
Chemical Substances	Calcium (SY7Q814VUP) ; Calcium, Dietary
Language	English
Publishing date	2023-06-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2216564120
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Article: [New approved markers of bone turnover for osteoporosis in Japan].

Miki, Takami / Masaki, Hideki

Clinical calcium

2012 Volume 22, Issue 6, Page(s) 877–883

Abstract: Various markers of bone turnover are already under clinical use in Japan, and mostly for clinical investigation in some countries. Standard values including ranges and variations are summarized in the previous edition of the guideline. The information of ...

Abstract	Various markers of bone turnover are already under clinical use in Japan, and mostly for clinical investigation in some countries. Standard values including ranges and variations are summarized in the previous edition of the guideline. The information of additional new markers adapted by government is summarized including clinical features in the new edition 2012. Among the new markers, the methods for measurement for TRACP-5b and ucOC are developed in Japan. As P1NP and TRACP-5b levels are not affected by meals, biological variations are smaller compared with other markers. ucOC is unique because it is to evaluate vitamin K insufficiency for bone. New bone markers adapted in the Japanese guideline 2012 will facilitate clinicians to utilize of metabolic markers of bone for osteoporosis treatment.
MeSH term(s)	Acid Phosphatase/blood ; Biomarkers/blood ; Bone and Bones/metabolism ; Humans ; Isoenzymes/blood ; Japan ; Osteocalcin/blood ; Osteoporosis/blood ; Osteoporosis/diagnosis ; Practice Guidelines as Topic ; Tartrate-Resistant Acid Phosphatase
Chemical Substances	Biomarkers ; Isoenzymes ; Osteocalcin (104982-03-8) ; ACP5 protein, human (EC 3.1.3.2) ; Acid Phosphatase (EC 3.1.3.2) ; Tartrate-Resistant Acid Phosphatase (EC 3.1.3.2)
Language	Japanese
Publishing date	2012-06
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2386417-5
ISSN	0917-5857
ISSN	0917-5857
DOI	CliCa1206877883
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Article ; Online: Hypoblast from human pluripotent stem cells regulates epiblast development.

Nature

2023 Volume 626, Issue 7998, Page(s) 357–366

Abstract: Recently, several studies using cultures of human embryos together with single-cell RNA-seq analyses have revealed differences between humans and mice, necessitating the study of human ... ...

Abstract	Recently, several studies using cultures of human embryos together with single-cell RNA-seq analyses have revealed differences between humans and mice, necessitating the study of human embryos
MeSH term(s)	Humans ; Cell Differentiation ; Embryo Implantation ; Embryo, Mammalian/cytology ; Embryo, Mammalian/embryology ; Embryo, Mammalian/metabolism ; Embryonic Development/genetics ; Embryonic Development/physiology ; Germ Layers/cytology ; Germ Layers/embryology ; Germ Layers/metabolism ; Pluripotent Stem Cells/cytology ; Interleukin-6/metabolism ; Gastrula/cytology ; Gastrula/embryology ; Amnion/cytology ; Amnion/embryology ; Amnion/metabolism ; Ectoderm/cytology ; Ectoderm/embryology ; Ectoderm/metabolism ; Intercellular Signaling Peptides and Proteins/genetics ; Intercellular Signaling Peptides and Proteins/metabolism ; Otx Transcription Factors/genetics ; Otx Transcription Factors/metabolism
Chemical Substances	Interleukin-6 ; DKK1 protein, human ; OTX2 protein, human ; IL6 protein, human ; Intercellular Signaling Peptides and Proteins ; Otx Transcription Factors
Language	English
Publishing date	2023-12-05
Publishing country	England
Document type	Journal Article
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-023-06871-2
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Article: [Bone and calcium metabolism in elderly women].

Masaki, Hideki / Miki, Takami

Clinical calcium

2011 Volume 21, Issue 9, Page(s) 1361–1367

Abstract: Bone mass of elderly women reduces after menopause, but the rate of reduction differ individually especially in the elderly, because bone metabolism of the elderly is influenced by many factors such as hormones, fractures, drugs, ability of exercise and/ ... ...

Abstract	Bone mass of elderly women reduces after menopause, but the rate of reduction differ individually especially in the elderly, because bone metabolism of the elderly is influenced by many factors such as hormones, fractures, drugs, ability of exercise and/or nutritional level. Therefore, it is quite difficult to determine the normal ranges of the metabolism. As a whole, aging accelerates bone turnover slowly with wide range of individual variation. Subnormal renal function may effect on the excretion or metabolism of bone markers, such as osteocalcin. Urinary markers such as NTX corrected by urinary creatinine may be higher than the real level, because of low creatinine production in the elderly. These factors may influence on the elevated bone metabolism resulting in the discrepancy with morphometric evaluation.
MeSH term(s)	Aged ; Aged, 80 and over ; Aging/genetics ; Aging/metabolism ; Biomarkers ; Bone and Bones/metabolism ; Calcium/metabolism ; Collagen Type I/urine ; Creatinine/urine ; Estrogens/metabolism ; Estrogens/physiology ; Female ; Glucuronidase/genetics ; Humans ; Kidney/metabolism ; Osteocalcin/metabolism ; Peptides/urine ; Polymorphism, Genetic ; Vitamin K Deficiency
Chemical Substances	Biomarkers ; Collagen Type I ; Estrogens ; Peptides ; collagen type I trimeric cross-linked peptide ; Osteocalcin (104982-03-8) ; Creatinine (AYI8EX34EU) ; Glucuronidase (EC 3.2.1.31) ; klotho protein (EC 3.2.1.31) ; Calcium (SY7Q814VUP)
Language	Japanese
Publishing date	2011-09
Publishing country	Japan
Document type	English Abstract ; Journal Article ; Review
ZDB-ID	2386417-5
ISSN	0917-5857
ISSN	0917-5857
DOI	CliCa110913611367
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Article ; Online: Bazedoxifene improves renal function and increases renal phosphate excretion in patients with postmenopausal osteoporosis.

Masaki, Hideki / Imanishi, Yasuo / Naka, Hiroshi / Nagata, Yuki / Kurajoh, Masafumi / Mori, Katsuhito / Emoto, Masanori / Miki, Takami / Inaba, Masaaki

Journal of bone and mineral metabolism

2020 Volume 38, Issue 3, Page(s) 405–411

Abstract: Introduction: Because aging is a predictor of renal insufficiency in the general population, renal function is a concern in postmenopausal patients undergoing treatment for osteoporosis. Although high serum phosphate concentration is a predictor of ... ...

Abstract	Introduction: Because aging is a predictor of renal insufficiency in the general population, renal function is a concern in postmenopausal patients undergoing treatment for osteoporosis. Although high serum phosphate concentration is a predictor of renal insufficiency, the effect of selective estrogen receptor modulator (SERM) on renal function and phosphate homeostasis remains to be established. Materials and methods: We administered 20 mg/day bazedoxifene to 48 postmenopausal osteoporotic women who had been taking alfacalcidol for ≥ 6 months, and assessed lumbar spine bone mineral density (LS-BMD), renal function (by calculating estimated glomerular filtration rate using serum cystatin-C levels [eGFRcys] [range 38.0-98.2 mL/min/1.73 m Results: LS-BMD was significantly higher 6 months after the initiation of bazedoxifene administration. eGFRcys had increased by 3 months after initiation and was stable until 12 months. Serum phosphate gradually decreased after initiation, reaching statistical significance at 6 months. The changes in serum phosphate were also significant when the maximum tubular reabsorption rate of phosphate was normalized to glomerular filtration rate (TmP/GFR), indicating that bazedoxifene treatment reduces serum phosphate by increasing the urinary excretion of phosphate. The change in eGFRcys after the initiation of bazedoxifene was significantly negatively correlated with the change in serum phosphate, suggesting that a reduction in serum phosphate improves renal function. Conclusion: Bazedoxifene improves renal function, possibly by increasing renal phosphate excretion, in postmenopausal osteoporotic women without severe renal insufficiency.
MeSH term(s)	Aged ; Bone Density/drug effects ; Female ; Fibroblast Growth Factors/blood ; Glomerular Filtration Rate/drug effects ; Homeostasis ; Humans ; Indoles/pharmacology ; Indoles/therapeutic use ; Kidney/drug effects ; Kidney/physiopathology ; Linear Models ; Osteoporosis, Postmenopausal/blood ; Osteoporosis, Postmenopausal/drug therapy ; Osteoporosis, Postmenopausal/physiopathology ; Osteoporosis, Postmenopausal/urine ; Parathyroid Hormone/blood ; Phosphates/blood ; Phosphates/urine
Chemical Substances	Indoles ; Parathyroid Hormone ; Phosphates ; Fibroblast Growth Factors (62031-54-3) ; fibroblast growth factor 23 (7Q7P4S7RRE) ; bazedoxifene (Q16TT9C5BK)
Language	English
Publishing date	2020-01-02
Publishing country	Japan
Document type	Clinical Trial ; Journal Article
ZDB-ID	1295123-7
ISSN	1435-5604 ; 0914-8779
ISSN (online)	1435-5604
ISSN	0914-8779
DOI	10.1007/s00774-019-01073-1
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Article: [New development in bisphosphonate treatment. Bisphosphonates and gastrointestinal adverse effects].

Miki, Takami / Masaki, Hideki

Clinical calcium

2009 Volume 19, Issue 1, Page(s) 91–97

Abstract: Endoscopic examination suggested gastric mucosal damage by NSAID is more serious than that of bisphosphonates. In addition, the incidence of GI-adverse effects (AEs) is reported to be insignificant, if the incidence is adjusted by history of peptic ulcer, ...

Abstract	Endoscopic examination suggested gastric mucosal damage by NSAID is more serious than that of bisphosphonates. In addition, the incidence of GI-adverse effects (AEs) is reported to be insignificant, if the incidence is adjusted by history of peptic ulcer, drugs for comorbidity, sex, age and/or ways of evaluation of the AEs. The anxiety for taking medication under empty stomach may contribute to the increase of GI-AEs. Some consideration must be taken for patients with past history of peptic ulcer, and/or drug user such as NSAIDs.
MeSH term(s)	Animals ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Bone Density Conservation Agents/administration & dosage ; Bone Density Conservation Agents/adverse effects ; Dinoprostone/metabolism ; Diphosphonates/administration & dosage ; Diphosphonates/adverse effects ; Female ; Fibroblast Growth Factors/metabolism ; Gastrointestinal Diseases/chemically induced ; Gastrointestinal Diseases/pathology ; Humans ; Male ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Bone Density Conservation Agents ; Diphosphonates ; Vascular Endothelial Growth Factor A ; Fibroblast Growth Factors (62031-54-3) ; Dinoprostone (K7Q1JQR04M)
Language	Japanese
Publishing date	2009-01
Publishing country	Japan
Document type	English Abstract ; Journal Article ; Review
ZDB-ID	2386417-5
ISSN	0917-5857
ISSN	0917-5857
DOI	CliCa09019197
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