*Subtitles available in both English and Japanese.

Complete remission of STZ diabetes by removing “Diabetes Stem Cells.”

Abnormal hematopoietic stem cells named “Diabetes Stem Cells (DSC)” were found to inhibit islet regeneration in STZ mice and prevent diabetes remission. Combining insulin with an HDAC inhibitor for a certain period removed the “Diabetes Stem Cells,” leading to complete remission of diabetes.

*ENDO2024 (Endocrine Society2024), 4th Edition of World Congress on Endocrinology, Diabetes and Metabolism, and Communications Biology 2003

Introduction to papers on “Diabetes Stem Cells.”

 Our research reports on bone marrow-derived cells in diabetes and its complications

Our research reports on bone marrow-derived cells in diabetes and its complications (2003-2024).

Research reports on abnormalities in bone marrow-derived cells and organ damage in diabetes over the past 20 years are summarized by organ. Each paper provides insights into how these abnormalities are related to diabetes.

– Skeletal –

– Appetite –

– Circulation –

– Energy –

– Metabolism –

– Nutrition –

– Sensory –

– Whole Body –

– Excretion –

– Infection –

– Bone Marrow –

Introduction to Related Papers

At ENDO2024 in Boston (2024)
At ENDO2024 in Boston (2024)

Related Paper Achievements (2020 – 2024)

2023

Impaired circadian rhythm may disturb epithelialization in the wound healing of the skin in diabetic mice. Okano J, Katagi M, Nakagawa T, Kojima H. J Dermatol Sci. 2023 Apr;110(1):31-34. doi: 10.1016/j.jdermsci.2023.03.005. Epub 2023 Mar 21. PMID: 37012132.

Complete remission of diabetes with a transient HDAC inhibitor and insulin in streptozotocin mice. Kojima H, Katagi M, Okano J, Nakae Y, Ohashi N, Fujino K, Miyazawa I, Nakagawa T. Commun Biol. 2023 Jun 13;6(1):637. doi: 10.1038/s42003-023-05010-x. PMID: 37311905; PMCID: PMC10264456.

Expression of proinflammatory cytokines and proinsulin by bone marrow-derived cells for fracture healing in long-term diabetic mice. Fujikawa H, Kojima H, Terashima T, Katagi M, Yayama T, Kumagai K, Mori K, Saito H, Imai S. BMC Musculoskelet Disord. 2023 Jul 18;24(1):585. doi: 10.1186/s12891-023-06710-5. PMID: 37464323; PMCID: PMC10355075.

Aberrant bone marrow-derived microglia in the hypothalamus may dysregulate appetite in diabetes. Katagi M, Nakae Y, Okano J, Fujino K, Tanaka T, Miyazawa I, Ohashi N, Nakagawa T, Kojima H. Biochem Biophys Res Commun. 2023 Nov 19;682:132-137. doi: 10.1016/j.bbrc.2023.09.083. Epub 2023 Sep 27. PMID: 37806251.

2022

Ambient temperature is correlated with the severity of neonatal hypoxic- ischemic brain injury via microglial accumulation in mice. Zen R, Terashima T, Tsuji S, Katagi M, Ohashi N, Nobuta Y, Higuchi A, Kanai H, Murakami T, Kojima H. Frontiers in Pediatrics. May 06, 2022.

Bone marrow-derived inducible microglia-like cells ameliorate motor function and survival in a mouse model of amyotrophic lateral sclerosis. Kobashi S, Terashima T, Katagi M, Urushitani M, Kojima H. Cytotherapy, April 04, 2022.

2021

GLT1 gene delivery based on bone marrow-derived cells ameliorates motor function and survival in a mouse model of ALS. Ohashi N, Terashima T, Katagi M, Nakae Y, Okano J, Suzuki Y, Kojima H. Sci Rep, 11, 12803, 2021.

Malfunctioning CD106-positive, short-term hematopoietic stem cells trigger diabetic neuropathy in mice by cell fusion. Katagi M, Terashima T, Ohashi N, Nakae Y, Yamada A, Nakagawa T, Miyazawa I, Maegawa H, Okano J, Suzuki Y, Fujino K, Eguchi Y, Kojima H. Commun Biol, 4, 575, 2021.

A novel role for bone marrow-derived cells to recover damaged keratinocytes from radiation-induced injury. Okano J, Nakae Y, Nakagawa T, Katagi M, Terashima T, Nagakubo D, Nakayama T, Yoshie O, Suzuki Y, Kojima H. Sci Rep, 11, 5653, 2021.

2020

Enhancing the Therapeutic Efficacy of Bone Marrow-Derived Mononuclear Cells with Growth Factor-Expressing Mesenchymal Stem Cells for ALS in Mice. Terashima T, Kobashi S, Watanabe Y, Nakanishi M, Honda N, Katagi M, Ohashi N, Kojima H. iScience, 23(11), 101764, 2020.

Bone marrow-derived mononuclear cells relieve neuropathic pain after spinal nerve injury in mice. Takamura H, Terashima T, Mori K, Katagi M, Okano J, Suzuki Y, Imai S, Kojima H. Mol Ther Methods Clin Dev, 17, 657-665, 2020.

Transplantation of M2-deviated microglia promotes recovery of motor function after spinal cord injury in mice. Kobashi S, Terashima T, Katagi M, Nakae Y, Okano J, Suzuki Y, Urushitani M, Kojima H. Mol Ther, 28, 254-265, 2020.

Department of Biochemistry and Molecular Biology, Division of Regenerative and Reparative Medicine (as of 2019)
Department of Biochemistry and Molecular Biology, Division of Regenerative and Reparative Medicine (as of 2019)

Related Paper Achievements (2015 – 2019)

2019

Dynamics of host and graft after cell sheet transplantation: basic study for the application of amyotrophic lateral sclerosis. Nakanishi M, Watanabe Y, Honda N, Une M, Kazuki K, Kazuki Y, Terashima T, Katagi M, Nakashima K, Hanajima R. Brain Res, 1724, 146444, 2019.

Advanced technology for gene delivery with homing peptides to spinal cord through systemic circulation in mice. Terashima T, Ogawa N, Sato T, Katagi M, Nakae Y, Okano J, Maegawa H, Kojima H. Mol Ther Methods Clin Dev, 13, 474-483, 2019.

Efficient Prostate Cancer Therapy with Tissue-Specific Homing Peptides Identified by Advanced Phage Display Technology. Wada A, Terashima T, Kageyama S, Yoshida T, Narita M, Kawauchi A, Kojima H. Mol Ther Oncolytics, 12, 138-146, 2019.

A role for bone marrow-derived cells in diabetic nephropathy. Nobuta H, Katagi M, Kume S, Terashima T, Araki SI, Maegawa H, Kojima H, Nakagawa T. FASEB J., 33, 4067-76, 2019.

2018

Stem cell factor induces polarization of microglia to the neuroprotective phenotype in vitro. Terashima T, Nakae Y, Katagi M, Okano J, Suzuki Y, Kojima H. Heliyon, Volume 4, Issue 10, e00837, 2018.

Gene therapy for neuropathic pain using dorsal root ganglion-targeted helper-dependent adenoviral vectors with GAD67 expression. Ogawa N, Terashima T, Oka K, Chan L, Kojima H. PAIN Reports, 3, e695, 2018.

Gene Therapy for Neuropathic Pain through siRNA-IRF5 Gene Delivery with Homing Peptides to Microglia. Terashima T, Ogawa N, Nakae Y, Sato T, Katagi M, Okano J, Maegawa H, Kojima H. Mol Ther Nucleic Acids., 11, 203-215, 2018.

2017

Charcot-Marie-Tooth disease type 2A with an autosomal-recessive inheritance: the first report of an adult-onset disease. Hikiami R, Yamashita H, Koita N, Jingami N, Sawamoto N, Furukawa K, Kawai H, Terashima T, Oka N, Hashiguchi A, Takashima H, Urushitani M, Takahashi R. J Hum Genet. Epub 2017 Nov 13.

2016

Hyperglycemia Induces Skin Barrier Dysfunctions with Impairment of Epidermal Integrity in Non-Wounded Skin of Type 1 Diabetic Mice. Okano J, Kojima H, Katagi M, Nakagawa T, Nakae Y, Terashima T, Kurakane T, Kubota M, Maegawa H, Udagawa J. PLoS One, 11, e0166215, 2016.

Clinical Phenotype and Segregation of Mitochondrial 3243A>G Mutation in 2 Pairs of Monozygotic Twins. Maeda K, Kawai H, Sanada M, Terashima T, Ogawa N, Idehara R, Makiishi T, Yasuda H, Sato S, Hoshi K, Yahikozawa H, Nishi K, Itoh Y, Ogasawara K, Tomita K, Indo HP, Majima HJ. JAMA Neurol., 73, 990-3, 2016.

Ablation of a small subpopulation of diabetes-specific bone marrow-derived cells in mice protects against diabetic neuropathy. Urabe H, Terashima T, Kojima H, Chan L. Am. J. Physio.l Endocrinol. Metab., 310, E269-75, 2016.

Late-onset spinal form xanthomatosis without brain lesion: a case report. Yanagihashi M, Kano O, Terashima T, Kawase Y, Hanashiro S, Sawada M, Ishikawa Y, Shiraga N, Ikeda K, Iwasaki Y. BMC Neurol., 16, 21, 2016

2015

Proinsulin-producing, hyperglycemia-induced adipose tissue macrophages underlie insulin resistance in high fat-fed diabetic mice. Buras ED, Yang L, Saha P, Kim J, Mehta P, Yang Y, Hilsenbeck S, Kojima H, Chen W, Smith CW, Chan L. FASEB J., 29, 3537-48, 2015.

Epidermis-dermis junction as a novel location for bone marrow-derived cells to reside in response to ionizing radiation. Okano J, Kojima H, Katagi M, Nakae Y, Terashima T, Nakagawa T, Kurakane T, Okamoto N, Morohashi K, Maegawa H, Udagawa J. Biochem. Biophys. Res. Commun., 461, 695-701, 2015.

Bone marrow-derived TNF-α causes diabetic neuropathy in mice. Urabe H, Terashima T, Lin F, Kojima H, Chan L. Diabetologia, 58, 402-10, 2015.

Department of Biochemistry and Molecular Biology, Division of Regenerative and Reparative Medicine (as of 2014)
Department of Biochemistry and Molecular Biology, Division of Regenerative and Reparative Medicine (as of 2014)

Related Paper Achievements (2010 – 2014)

2014

Emerging roles of hematopoietic cells in the pathobiology of diabetic complications. Kojima H, Kim J, Chan L. Trends Endocrinol. Metab., 25, 178-87, 2014.

Stem Cell Factor-Activated Bone Marrow Ameliorates Amyotrophic Lateral Sclerosis by Promoting Protective Microglial Migration. Terashima T, Kojima H, Urabe H, Yamakawa I, Ogawa N, Kawai H, Chan L, Maegawa H. J. Neurosci. Res., 92, 856-69, 2014.

Hyperglycemia induces abnormal gene expression in hematopoietic stem cells and their progeny in diabetic neuropathy. Katagi M, Terashima T, Okano J, Urabe H, Nakae Y, Ogawa N, Udagawa J, Maegawa H, Matsumura K, Chan L, Kojima H. FEBS letters, 588, 1080-6, 2014.

Gene therapy for neuropathic pain by silencing of TNF-α expression with lentiviral vectors targeting the dorsal root ganglion in mice. Ogawa N, Kawai H, Terashima T, Kojima H, Oka K, Chan L, Maegawa H. PLoS One, 9, e92073, 2014.

A mutation of COX6A1 causes a recessive axonal or mixed form of Charcot-Marie-Tooth disease. Tamiya G, Makino S, Hayashi M, Abe A, Numakura C, Ueki M, Tanaka A, Ito C, Toshimori K, Ogawa N, Terashima T, Maegawa H, Yanagisawa D, Tooyama I, Tada M, Onodera O, Hayasaka K. Am. J. Hum. Genet., 95, 294-300, 2014.

Polyglycerol-functionalized nanodiamond as a platform for gene delivery: Derivatization, characterization, and hybridization with DNA. Zhao L, Nakae Y, Qin H, Ito T, Kimura T, Kojima H, Chan L, Komatsu N. Beilstein J. Org. Chem., 10, 707-13, 2014.

2013

Haematopoietic cells produce BDNF and regulate appetite upon migration to the hypothalamus. Urabe H, Kojima H, Chan L, Terashima T, Ogawa N, Katagi M, Fujino K, Kumagai A, Kawai H, Asakawa A, Inui A, Yasuda H, Eguchi Y, Oka K, Maegawa H, Kashiwagi A, Kimura H. Nat. Commun., 4, 1526, 2013.

2012

Interleukin-7 induces recruitment of monocytes/macrophages to endothelium. Li R, Paul A, Ko KW, Sheldon M, Rich BE, Terashima T, Dieker C, Cormier S, Li L, Nour EA, Chan L, Oka K. Eur. Heart J., 33, 3114-23, 2012.

Bone marrow expression of poly(ADP-ribose) polymerase underlies diabetic neuropathy via hematopoietic-neuronal cell fusion. Terashima T, Kojima H, Chan L. FASEB J., 26, 295-308, 2012.

Brain-Derived Neurotrophic Factor from Bone Marrow-Derived Cells Promotes Post-Injury Repair of Peripheral Nerve. Takemura Y, Imai S, Kojima H, Katagi M, Yamakawa I, Kasahara T, Urabe H, Terashima T, Yasuda H, Chan L, Kimura H, Matsusue Y. PLoS One, 7, e44592, 2012.

2011

Pathogenesis of diabetic neuropathy: bad to the bone. Chan L, Terashima T, Urabe H, Lin F, Kojima H. Endocrinol. Metab., 301, E844-852, 2011.

Transfer of bone marrow progenitors prevents coronary insufficiency and systolic dysfunction in the mechanical unloaded heart in mice. Koike M, Kojima H, Fujimiya M, Matsubayashi K, Aimi Y, Kimura H, Asai T. J. Surg. Res., 171, 47-57, 2011.

Inactivation of TNF-α Ameliorates Diabetic Neuropathy in Mice. Yamakawa I, Kojima H, Terashima T, Katagi M, Oi J, Urabe H, Sanada M, Kawai H, Chan L, Yasuda H, Maegawa H, Kimura H. Am. J. Physiol. Ann. NY. Acad. Sci., 1240, 70-76, 2011.

Pathogenesis of diabetic neuropathy: bad to the bone. Chan L, Terashima T, Urabe H, Lin F, Kojima H. Ann. NY. Acad. Sci., 1240, 70-76, 2011.

Homing of the bone marrow-derived interstitial cells of Cajal is decreased in diabetic mouse intestine. Li Y, Kojima H, Fujino K, Matsumura K, Katagi M, Urabe H, Chan L, Eguchi Y, Zhao L, Kimura H. J. Gastroenterol. Hepatol., 26, 1072-8, 2011.

2010

Chronic foot-shock stress potentiates the influx of bone marrow-derived microglia into hippocampus. Brevet M, Kojima H, Asakawa A, Atsuchi K, Ushikai M, Ataka K, Inui A, Kimura H, Sevestre H, Fujimiya M. J. Neurosci. Res., 88, 1890-7, 2010.

Hyperglycemia induces oxidative stress and impairs axonal transport rates in mice. Sharma R, Buras E, Terashima T, Serrano F, Massaad CA, Hu L, Bitner B, Inoue T, Chan L, Pautler RG. PLoS One, 5, e13463, 2010.

Malfunction of bone marrow-derived osteoclasts and the delay of bone fracture healing in diabetic mice. Kasahara T, Imai S, Kojima H, Katagi M, Kimura H, Chan L, Matsusue Y. Bone, 47(3):617-25, 2010.

Shiga University of Medical Science
Shiga University of Medical Science

Related Paper Achievements (2005 – 2009)

2009

Neurogenin3 is sufficient for transdetermination of hepatic progenitor cells into neo-islets in vivo but not transdifferentiation of hepatocytes. Yechoor V, Liu V, Espiritu C, Paul A, Oka K, Kojima H, Chan L. Dev. Cell, 16, 358-73, 2009.

Pathological roles of bone marrow-derived stellate cells in a mouse model of alcohol-induced fatty liver. Fujimiya T, Liu J, Kojima H, Shirafuji S, Kimura H, Fujimiya M. Am. J. Physiol. Gastrointest. Liver Physiol., 297, G451-60, 2009.

A neuronal VLDLR variant lacking the third complement-type repeat exhibits high capacity binding of apoE containing lipoproteins. Sakai K, Tiebel O, Ljungberg MC, Sullivan M, Lee HJ, Terashima T, Li R, Kobayashi K, Lu HC, Chan L, Oka K. Brain Research., 18, 11-21, 2009.

DRG-targeted helper-dependent adenoviruses mediate selective gene delivery for therapeutic rescue of sensory neuronopathies in mice. Terashima T, Oka K, Kritz AB, Kojima H, Baker AH, Chan L. J. Clin. Invest., 119, 2100-2112, 2009.

2008

Isolation of specific peptides that home to dorsal root ganglion neurons in mice. Oi J, Terashima T, Kojima H, Fujimiya M, Maeda K, Arai R, Chan L, Yasuda H, Kashiwagi A, Kimura H. Neuroscience Letters., 43, 266-72, 2008.

2007

T2*-weighted MR images of a patient with familial cerebral cavernous malformation. Maeda K, Terashima T, Kawai H, Sanada M. Intern. Med., 46, 541-2, 2007.

Rationale and usefulness of newly devised abbreviated diagnostic criteria and staging for diabetic polyneuropathy. Yasuda H, Sanada M, Kitada K, Terashima T, Kim H, Sakaue Y, Fujitani M, Kawai H, Maeda K, Kashiwagi A.Diabetes Res. Clin. Pract., 77 Suppl. 1: 78-83, 2007.

2006

Chronic Diabetic Complications: The Body’s Adaptive Response to Hyperglycemia Gone Awry? Chan L, Terashima T, Fujimiya M, and Kojima H. Trans. Am. Clin. Climatol. Assoc., 117: 341-352, 2006.

Paraneoplastic cerebellar degeneration in olfactory neuroepithelioma. Maeda K, Sasaki T, Murata Y, Terashima T, Kawai H, Yasuda H, Okabe H, Tanaka K. J. Neurol. Neurosurg. Psychiatry., 77, 123-124, 2006.

Extrapancreatic Proinsulin/Insulin-expressing Cells in Diabetes Mellitus: Is History Repeating Itself? Kojima H, Fujimiya M, Terashima T, Kimura H, Chan L. Endocr. J., 53, 715-722, 2006.

2005

The fusion of bone-marrow-derived proinsulin-expressing cells with nerve cells underlies diabetic neuropathy. Terashima T, Kojima H, Fujimiya M, Matsumura K, Oi J, Hara M, Kashiwagi A, Kimura H, Yasuda H, Chan L. Proc. Natl. Acad. Sci. U.S.A. 102, 12525-12530, 2005.

Antiganglion neuron antibodies correlate with neuropathy in Sjögren syndrome. Murata Y, Maeda K, Kawai H, Terashima T, Okabe H, Kashiwagi A, Yasuda H. NeuroReport, 16: 677-681, 2005.

Aerial Photo of Shiga University of Medical Science
Aerial Photo of Shiga University of Medical Science

Related Paper Achievements (2000 – 2004)

2004

Metabolic adaptations in the absence of perilipin: increased beta-oxidation and decreased hepatic glucose production associated with peripheral insulin resistance but normal glucose tolerance in perilipin-null mice. Saha PK, Kojima H, Martinez-Botas J, Sunehag AL, Chan L. J. Biol. Chem., 279, 35150-35158, 2004.

Extrapancreatic insulin-producing cells in multiple organs in diabetes. Kojima H, Fujimiya M, Matsumura K, Nakahara T, Hara M, Chan L. Proc. Natl. Acad. Sci. U. S. A., 101, 2458-2463, 2004.

2003

NeuroD-betacellulin gene therapy induces islet neogenesis in the liver and reverses diabetes in mice. Kojima H, Fujimiya M, Matsumura K, Younan P, Imaeda H, Maeda M, Chan L. Nat. Med., 9, 596-603, 2003.

2002

Combined Expression of Pancreatic Duodenal Homeobox 1 and lslet Factor 1 Induces Immature Enterocytes to Produce Insulin,Kojima H, Nakamura T, Fujita Y, Kishi A, Fujimiya M, Yamada S, Kudo M, Nishio Y, Maegawa H, Haneda M, Yasuda H, Kojima I, Seno M, Norman CW.Wong, Kikkawa R, Kashiwagi A. Diabetes, 51, 1398-1408, 2002.

Increased beta-oxidation but no insulin resistance or glucose intolerance in mice lacking adiponectin. Ma K, Cabrero A, Saha PK, Kojima H, Li L, Chang BH, Paul A, Chan L. J. Biol. Chem., 277, 34658-34661, 2002.

SUMO-1 co-localized with mutant atrophin-1 with expanded polyglutamines accelerates intranuclear aggregation and cell death. Terashima T, Kawai H, Fujitani M, Maeda K, Yasuda H. NeuroReport, 13: 2359-2364, 2002.

2001

Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption. Lee MH, Lu K, Hazard S, Yu H, Shulenin S, Hidaka H, Kojima H, Allikmets R, Sakuma N, Pegoraro R, Srivastava AK, Salen G, Dean M, Patel SB. Nat. Genet., 27, 79-83, 2001.

Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2, encoded by ABCG5 and ABCG8, respectively. Lu K, Lee MH, Hazard S, Brooks-Wilson A, Hidaka H, Kojima H, Ose L, Stalenhoef AF, Mietinnen T, Bjorkhem I, Bruckert E, Pandya A,Brewer HB Jr, Salen G, Dean M, Srivastava A, Patel SB. Am. J. Hum. Genet., 69, 278-290, 2001.

Fine mapping of a gene responsible for regulating dietary cholesterol absorption; founder effects underlie cases of phytosterolaemia in multiple communities. Lee MH, Gordon D, Ott J, Lu K, Ose L, Miettinen T, Gylling H, Stalenhoef AF, Pandya A, Hidaka H, Brewer B Jr, Kojima H, Sakuma N, Pegoraro R, Salen G, Patel SB. Eur. J. Hum. Genet., 9, 375-384, 2001.

Differentiation of immature enterocytes into enteroendocrine cells by Pdx1 overexpression, Yamada S, Kojima H, Fujimiya M, Nakamura T, Kashiwagi A, Kikkawa R. Am. J. Physiol. Gastrointest. Liver Physiol., 281, G229-G236, 2001.

Expression of Rho-family GTPases (Rac, cdc42, RhoA) and their association with p-21 activated kinase in adult rat peripheral nerve. Terashima T, Yasuda H, Terada M, Kogawa S, Maeda K, Haneda M, Kashiwagi A, Kikkawa R. J. Neurochem., 77: 986-992, 2001.

Laboratory

About the Lab

Applying the unique technology developed by Professor Kojima, efforts include the redevelopment of existing drugs, development of new drugs, and etc.

Message from Professors

Research is conducted daily to understand why diseases do not heal, find answers, and develop cures rather than treatments.

Members

Introducing the research course and related members. Detailed information on each member’s expertise, research content, and achievements is provided.

Joint Research

Research commissioned by Biozipcode Inc. and conducted by Shiga University of Medical Science faculty. Expenses are covered by the commissioning party.

Publications

A list of papers published by the lab is available. Research outcomes led by Special Professor Kojima in diabetes and regenerative medicine are presented.

Access

Directions to Shiga University of Medical Science and the lab. Note: JR Seta Station does not accommodate express trains. Please use rapid or local trains.

FAQ

Frequently asked questions about the Department of Regenerative Medicine, diabetes stem cells, and research content are compiled.

Are You Interested in Research at the Department of Regenerative Medicine?

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