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A New Concept of Stem Cell Disorders, and the Rationale for Transplantation of Normal Stem Cells

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Part of the book series: Stem Cells and Cancer Stem Cells ((STEM,volume 2))

Abstract

There are at least two types of stem cells in the bone marrow of mice and humans: hemopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). As all cells in the body are differentiated from HSCs or MSCs, it is conceivable that all diseases originate from disorders in these cells. We here provide evidence that most diseases are, in fact, stem cell disorders, and that a newly developed method of bone marrow transplantation (BMT) can be used to prevent and treat most intractable diseases, since it permits the recipient’s abnormal HSCs and MSCs to be replaced with the donor’s normal HSCs and MSCs.

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References

  • Adachi Y, Oyaizu H, Taketani S, Minamino K, Yamaguchi K, Shultz LD, Iwasaki M, Tomita M, Suzuki Y, Nakano K, Koike Y, Yasumizu R, Sata M, Hirama N, Kubota I, Fukuhara S, Ikehara S (2006) Treatment and transfer of emphysema by a new bone marrow transplantation method from normal mice to Tsk mice and vice versa. Stem Cells 24:2071–2077

    Article  PubMed  Google Scholar 

  • Appelbaum FR, Sandmaier B (2002) Sensitivity of renal cell cancer to nonmyeloablative allogeneic hematopoietic cell transplantations: unusual or unusually important? J ClinOncol 20:1965–1967

    Google Scholar 

  • Baron R, Harpaz I, Nemirovsky A, Cohen H, Monsonego A (2007) Immunity and neuronal repair in the progression of Alzheimer’s disease: a brief overview. Exp Gerontol 42:64–69

    Article  PubMed  CAS  Google Scholar 

  • Bregni M, Dodero A, Peccatori J, Pescarollo A, Bernardi M, Sassi I, Voena C, Zaniboni A, Bordignon C, Corradini P (2002) Nonmyeloablative conditioning followed by hematopoietic cell allografting and donor lymphocyte infusions for patients with metastatic renal and breast cancer. Blood 99:4234–4236

    Article  PubMed  CAS  Google Scholar 

  • Childs R, Chernoff A, Contentin N, Bahceci E, Schrump D, Leitman S, Read EJ, Tisdale J, Dunbar C, Linehan WM, Young NS, Barrett AJ (2000) Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med 343:750–758

    Article  PubMed  CAS  Google Scholar 

  • Esumi T, Inaba M, Ichioka N, Kushida T, Iida H, Ikehara S (2003) Successful allogeneic leg transplantation in rats in conjunction with intra-bone marrow injection of donor bone marrow cells. Transplantation 76:1543–1548

    Article  PubMed  CAS  Google Scholar 

  • Fernandes G, Alonso DR, Tanaka T, Thaler HT, Yunis EJ, Good RA (1983) Influence of diet on vascular lesions in autoimmune-prone B/W mice. Proc Natl Acad Sci USA 80:874–877

    Article  PubMed  CAS  Google Scholar 

  • Guo K, Inaba M, Li M, An J, Cui W, Song C, Wang J, Cui Y, Sakaguchi Y, Tsuda M, Omae M, Ando Y, Li Q, Wang X, Feng W, Ikehara S (2008) Long-term donor-specific tolerance in rat cardiac allografts by intrabone marrow injection of donor bone marrow cells. Transplantation 85:93–101

    Article  PubMed  Google Scholar 

  • Houghton J, Stoicov C, Nomura S, Rogers AB, Carlson J, Li H, Cai X, Fox JG, Goldenring JR, Wang TC (2004) Gastric cancer originating from bone marrow-derived cells. Science 306:1568–1571

    Article  PubMed  CAS  Google Scholar 

  • Ichioka N, Inaba M, Kushida T, Esumi T, Takahara K, Inaba K, Ogawa R, Iida H, Ikehara S (2002) Prevention of senile osteoporosis in SAMP6 mice by intrabone marrow injection of allogeneic bone marrow cells. Stem Cells 20:542–551

    Article  PubMed  Google Scholar 

  • Ikebukuro K, Adachi Y, Suzuki Y, Iwasaki M, Nakano K, Koike Y, Mukaide H, Yamada Y, Fujimoto S, Seino Y, Oyaizu H, Shigematsu A, Kiriyama N, Hamada Y, Kamiyama Y, Ikehara S (2006) Synergistic effects of injection of bone marrow cells into both portal vein and bone marrow on tolerance induction in transplantation of allogeneic pancreatic islets. Bone Marrow Transplant 38:657–664

    Article  PubMed  CAS  Google Scholar 

  • Ikehara S (1998) Autoimmune diseases as stem cell disorders: normal stem cell transplant for their treatment (review). Int J Mol Med 1:5–16

    PubMed  CAS  Google Scholar 

  • Ikehara S (2003) A new concept of stem cell disorders and their new therapy. J Hematother Stem Cell Res 12:643–653

    Article  PubMed  Google Scholar 

  • Ikehara S (2008) A novel method of bone marrow transplantation (BMT) for intractable autoimmune diseases. J Autoimmun 30:108–115

    Article  PubMed  Google Scholar 

  • Ikehara S, Good RA, Nakamura T, Sekita K, Inoue S, Oo MM, Muso E, Ogawa K, Hamashima Y (1985a) Rationale for bone marrow transplantation in the treatment of autoimmune diseases. Proc Natl Acad Sci USA 82:2483–2487

    Article  PubMed  CAS  Google Scholar 

  • Ikehara S, Ohtsuki H, Good RA, Asamoto H, Nakamura T, Sekita K, Muso E, Tochino Y, Ida T, Kuzuya H et al (1985b) Prevention of type I diabetes in nonobese diabetic mice by allogenic bone marrow transplantation. Proc Natl Acad Sci USA 82:7743–7747

    Article  PubMed  CAS  Google Scholar 

  • Ikehara S, Yasumizu R, Inaba M, Izui S, Hayakawa K, Sekita K, Toki J, Sugiura K, Iwai H, Nakamura T et al (1989) Long-term observations of autoimmune-prone mice treated for autoimmune disease by allogeneic bone marrow transplantation. Proc Natl Acad Sci USA 86:3306–3310

    Article  PubMed  CAS  Google Scholar 

  • Ikehara S, Kawamura M, Takao F, Inaba M, Yasumizu R, Than S, Hisha H, Sugiura K, Koide Y, Yoshida TO et al (1990) Organ-specific and systemic autoimmune diseases originate from defects in hematopoietic stem cells. Proc Natl Acad Sci USA 87:8341–8344

    Article  PubMed  CAS  Google Scholar 

  • Inaba M, Adachi Y, Hisha H, Hosaka N, Maki M, Ueda Y, Koike Y, Miyake T, Fukui J, Cui Y, Mukaide H, Koike N, Omae M, Mizokami T, Shigematsu A, Sakaguchi Y, Tsuda M, Okazaki S, Wang X, Li Q, Nishida A, Ando Y, Guo K, Song C, Cui W, Feng W, Katou J, Sado K, Nakamura S, Ikehara S (2007) Extensive studies on perfusion method plus intra-bone marrow–bone marrow transplantation using cynomolgus monkeys. Stem Cells 25:2098–2103

    Article  PubMed  Google Scholar 

  • Ishida T, Inaba M, Hisha H, Sugiura K, Adachi Y, Nagata N, Ogawa R, Good RA, Ikehara S (1994) Requirement of donor-derived stromal cells in the bone marrow for successful allogeneic bone marrow transplantation. Complete prevention of recurrence of autoimmune diseases in MRL/MP-Ipr/Ipr mice by transplantation of bone marrow plus bones (stromal cells) from the same donor. J Immunol 152:3119–3127

    PubMed  CAS  Google Scholar 

  • Kaneda H, Adachi Y, Saito Y, Ikebukuro K, Machida H, Suzuki Y, Minamino K, Zhang Y, Iwasaki M, Nakano K, Koike Y, Wang J, Imamura H, Ikehara S (2005) Long-term observation after simultaneous lung and intra-bone marrow–bone marrow transplantation. J Heart Lung Transplant 24:1415–1423

    Article  PubMed  Google Scholar 

  • Kawamura M, Hisha H, Li Y, Fukuhara S, Ikehara S (1997) Distinct qualitative differences between normal and abnormal hemopoietic stem cells in vivo and in vitro. Stem Cells 15:56–62

    Article  PubMed  CAS  Google Scholar 

  • Koike Y, Adachi Y, Suzuki Y, Iwasaki M, Koike-Kiriyama N, Minamino K, Nakano K, Mukaide H, Shigematsu A, Kiyozuka Y, Tubura A, Kamiyama Y, Ikehara S (2007) Allogeneic intrabone marrow–bone marrow transplantation plus donor lymphocyte infusion suppresses growth of colon cancer cells implanted in skin and liver of rats. Stem Cells 25:385–391

    Article  PubMed  Google Scholar 

  • Kushida T, Inaba M, Takeuchi K, Sugiura K, Ogawa R, Ikehara S (2000) Treatment of intractable autoimmune diseases in MRL/lpr mice using a new strategy for allogeneic bone marrow transplantation. Blood 95:1862–1868

    PubMed  CAS  Google Scholar 

  • Kushida T, Inaba M, Hisha H, Ichioka N, Esumi T, Ogawa R, Iida H, Ikehara S (2001) Intra-bone marrow injection of allogeneic bone marrow cells: a powerful new strategy for treatment of intractable autoimmune diseases in MRL/lpr mice. Blood 97:3292–3299

    Article  PubMed  CAS  Google Scholar 

  • Kushida T, Inaba M, Ikebukuro K, Ichioka N, Esumi T, Oyaizu H, Yoshimura T, Nagahama T, Nakamura K, Ito T, Hisha H, Sugiura K, Yasumizu R, Iida H, Ikehara S (2002) Comparison of bone marrow cells harvested from various bones of cynomolgus monkeys at various ages by perfusion or aspiration methods: a preclinical study for human BMT. Stem Cells 20:155–162

    Article  PubMed  Google Scholar 

  • Marmont AM (1994) Immune ablation followed by allogeneic or autologous bone marrow transplantation: a new treatment for severe autoimmune diseases? Stem Cells 12:125–135

    Article  PubMed  CAS  Google Scholar 

  • Nakamura T, Good RA, Yasumizu R, Inoue S, Oo MM, Hamashima Y, Ikehara S (1986) Successful liver allografts in mice by combination with allogeneic bone marrow transplantation. Proc Natl Acad Sci USA 83:4529–4532

    Article  PubMed  CAS  Google Scholar 

  • Nishimura M, Toki J, Sugiura K, Hashimoto F, Tomita T, Fujishima H, Hiramatsu Y, Nishioka N, Nagata N, Takahashi Y et al (1994) Focal segmental glomerular sclerosis, a type of intractable chronic glomerulonephritis, is a stem cell disorder. J Exp Med 179:1053–1058

    Article  PubMed  CAS  Google Scholar 

  • Oyaizu N, Yasumizu R, Miyama-Inaba M, Nomura S, Yoshida H, Miyawaki S, Shibata Y, Mitsuoka S, Yasunaga K, Morii S et al (1988) (NZW x BXSB)F1 mouse. A new animal model of idiopathic thrombocytopenic purpura. J Exp Med 167:2017–2022

    Article  PubMed  CAS  Google Scholar 

  • Petrini M, Pacini S, Trombi L, Fazzi R, Montali M, Ikehara S, Abraham NG (2009) Identification and purification of mesodermal progenitor cells from human adult bone marrow. Stem Cells Dev 18:857–866

    Article  PubMed  CAS  Google Scholar 

  • Ratajczak MZ, Kucia M, Reca R, Majka M, Janowska-Wieczorek A, Ratajczak J (2004) Stem cell plasticity revisited: CXCR4-positive cells expressing mRNA for early muscle, liver and neural cells ‘hide out’ in the bone marrow. Leukemia 18:29–40

    Article  PubMed  CAS  Google Scholar 

  • Rose N, Afanasyeva M (2003) Autoimmunity: busting the atherosclerotic plaque. Nat Med 9:641–642

    Article  PubMed  CAS  Google Scholar 

  • Suzuki Y, Adachi Y, Minamino K, Zhang Y, Iwasaki M, Nakano K, Koike Y, Ikehara S (2005) A new strategy for treatment of malignant tumor: intra-bone marrow–bone marrow transplantation plus CD4- donor lymphocyte infusion. Stem Cells 23:365–370

    Article  PubMed  Google Scholar 

  • Takada K, Inaba M, Ichioka N, Ueda Y, Taira M, Baba S, Mizokami T, Wang X, Hisha H, Iida H, Ikehara S (2006) Treatment of senile osteoporosis in SAMP6 mice by intra-bone marrow injection of allogeneic bone marrow cells. Stem Cells 24:399–405

    Article  PubMed  Google Scholar 

  • Than S, Ishida H, Inaba M, Fukuba Y, Seino Y, Adachi M, Imura H, Ikehara S (1992) Bone marrow transplantation as a strategy for treatment of non-insulin-dependent diabetes mellitus in KK-Ay mice. J Exp Med 176:1233–1238

    Article  PubMed  CAS  Google Scholar 

  • Thomas ED, Blume KG (1999) Historical markers in the development of allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 5:341–346

    Article  PubMed  CAS  Google Scholar 

  • Ueda Y, Inaba M, Takada K, Fukui J, Sakaguchi Y, Tsuda M, Omae M, Kushida T, Iida H, Ikehara S (2007) Induction of senile osteoporosis in normal mice by intra-bone marrow–bone marrow transplantation from osteoporosis-prone mice. Stem Cells 25:1356–1363

    Article  PubMed  CAS  Google Scholar 

  • Ueno NT, Rondon G, Mirza NQ, Geisler DK, Anderlini P, Giralt SA, Andersson BS, Claxton DF, Gajewski JL, Khouri IF, Korbling M, Mehra RC, Przepiorka D, Rahman Z, Samuels BI, Van Besien K, Hortobagyi GN, Champlin RE (1998) Allogeneic peripheral-blood progenitor-cell transplantation for poor-risk patients with metastatic breast cancer. J Clin Oncol 16:986–993

    PubMed  CAS  Google Scholar 

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Correspondence to Susumu Ikehara .

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Ikehara, S. (2012). A New Concept of Stem Cell Disorders, and the Rationale for Transplantation of Normal Stem Cells. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 2. Stem Cells and Cancer Stem Cells, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2016-9_4

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