Often known as “juvenile diabetes” or “insulin-deficiency diabetes mellitus”, type 1 diabetes is an autoimmune disease that often develops among children or teenagers. This life-long disease is caused by an inflammatory against beta cells in the pancreatic islets. These cells are responsible for the production and secretion of insulin. After they are damaged by an autoimmune inflammatory reaction, the body is unable to continue producing insulin. 

Unlike its type-2 counterpart, type 1 diabetes is characterized by a gradual and eventually complete deficiency in insulin production.

Symptoms of Type 1 Diabetes

During its early stages, type 1 diabetes causes increased thirst and urination, as well as extreme hunger and rapid weight loss. These symptoms occur as the body abruptly loses the ability to gain energy from sugars.

As the disease progresses into adulthood, more complications appear due to the accumulation of glucose across the organism. These include:

  • Progressive loss of vision
  • Recurrent or refractory infections, especially in the limbs
  • Kidney damage
  • Neuropathies

Traditional Management of Type 1 Diabetes

Patients with type 1 diabetes are in need of insulin administration for life, alongside frequent glucose monitoring that determines the insulin requirement that may be changed, and a tightly controlled diet regimen. Unfortunately, in most cases, Type 1 diabetes is diagnosed when all or most insulin production is terminated and then the disease is considered incurable. 

Theoretically, the disease can be cured by successful transplantation of pancreatic islets. However, this is an impractical solution to the problem: such treatments make sense for patients with type 1 diabetes with an indication for a kidney transplant, but kidney transplant could be accomplished alongside the harvesting of the pancreas or deceased donor’s pancreatic islet transplantation.

Mesenchymal Stem Cells for Reversing Type 1 Diabetes

New therapies are being developed that promise new options for people who are diagnosed very early with type 1 diabetes, during the so-called pre-diabetic stage. 

If the condition is caught before the complete and irreversible destruction of all the insulin-secreting cells, it may be possible to halt the autoimmune process and try to prevent complete destruction of all residual insulin-producing cells. Successful early treatment of pre-diabetes or patients diagnosed during the so-called “honeymoon period” justifies an attempt to apply innovative treatment against the autoimmune process responsible for destruction of pancreatic islets in order to save residual beta cells that could continue producing some insulin. Such patients can then use much lower levels of exogenous insulin, or sometimes even reverse their insulin dependence with adequate dietary control. 

At Biotherapy International, we believe that patients who still have residual insulin secreting cells may benefit from treatment with Mesenchymal Stromal Cell (MSCs) therapy. This type of treatment can be used to control the autoimmune-mediated inflammatory reaction that attacks the pancreatic beta cells, a process known as autoimmune insulitis.

This is still theoretical and not yet widely applicable clinically. Nevertheless, there is preliminary experimental evidence that in addition to well-documented therapeutic anti-inflammatory effects, MSCs may also be differentiated into insulin secreting cells. Unfortunately, this observation is still highly experimental and not yet applicable clinically. If this could be combined with the ability to turn off the autoimmune insulitis process, the overall process of type 1 diabetes may be theoretically reversed.

The capacity of MSCs to regulate immune-mediated inflammatory reactions may also help control glucose metabolism, lessen the amount of exogenous insulin needed, and also help to overcome insulin resistance that may develop in response to immune-mediated anti-insulin effects. Besides, control of anti-self-reactivity mediated by MSCs may also help minimize immune-mediated atherosclerosis which represents the main serious complication of type 1 diabetes. Diabetes-related arteriosclerosis can damage all patient’s essential organs including the brain, the heart, the eyes, the kidneys and peripheral blood vessels.

Our Scientific Findings on Diabetes

Scientific Research on Diabetes
Scientific Research on Autoimmune Diseases

 

  1. Slavin S, Strober S, Fuks Z, Kaplan HS.  Immunosuppression and organ transplantaton tolerance using total lymphoid irradiation (TLI). Diabetes 1980;29(Suppl 1):121-123.
  2. Britt LD, Scharp DW, Lacy PE, Slavin S.  Transplantation of islet cells across major histocompatibility barriers after total lymphoid irradiation and infusion of allogeneic bone marrow cells. Diabetes 1982;31(Suppl 4):63-68.
  3. Slavin S, Britt LD, Scharp DW, Lacy PE.  Treatment of experimental diabetes with histoincompatible islet allografts in rats conditioned with total lymphoid irradiation. In: Friedman EA, L’Esperance FA, Jr, eds. Diabetic Renal-Retinal Syndrome, 2: Prevention and Management. New York: Grune and Stratton 1982;519-528.
  4. Rossini AA, Slavin S, Woda BA, Geisberg M, Like AA, Mordes JP. Total lymphoid irradiation prevents diabetes mellitus in the bio-breeding/Worcester (BB/W) rat. Diabetes 1984;33:543-547.
  5. Slavin S, Weiss L, Weigensberg M, Morecki S, Fuks Z, Britt LD, Lacy PE, Scharp DW. Tolerance to alloantigens in rodents and reversal of streptozotocin-induced diabetes in tolerant rats by histoincompatible islet allografts. In: Shafrir E, Renold AE, eds. Lessons from Animal Diabetes. London: John Libbey 1985;606-609.
  6. Slavin S, Sidi H, Weiss L, Rosenmann E, Kalland T, Gross D.  Prevention of insulin-dependent diabetes mellitus (IDDM) and autoimmune insulitis in NOD mice by Linomide, a new immunoregulator of autoimmune diseases. EOS J Immunol Immunopharm 1993:XIII;129
  7. Slavin S, Sidi H, Weiss L, Rosenmann E, Kalland T, Gross D. Linomide – a new treatment for autoimmune diseases – the potential for treatment of type I diabetes. Diabetes Metabolism Reviews 1993;9(4):311-315.
  8. Gross DJ, Sidi H, Kalland T, Rosenmann E, Weiss L, Slavin S. Prevention of diabetes in non-obese diabetic mice by Linomide, a novel immunomodulating drug. Diabetologia 1994;37:1195-1201.
  9. Slavin S, Gross D, Weiss L.  Can diabetes be prevented in Type 1 diabetes? Diabetes Prevention & Therapy. 1995;9(2)15-16.
  10. Rapoport MJ, Weiss L, Mor A, Bistritzer T, Slavin S.
    Prevention of autoimmune diabetes by Linomide in NOD mice is associated with upregulation of the T cell receptor mediated activation of p21ras.  J of Immunology 1996;4721-4725.
  11. Gross D, Weiss L, Reibstein I, van den Brand J, Okamoto H, Clark A, Slavin S.  Amelioration of diabetes in NOD mice with advanced disease by Linomide induced immunoregulation combined with REG protein treatment. Endocrinology, 1998; 139:2369-74.
  12. Weiss L, Slavin S, Reich S, Cohen P, Shuster S, Stern R, Kaganovsky E, Okon E, Rubinstein AM, Naor D.  Induction of resistance to diabetes in non-obese diabetic mice by targeting CD44 with a specific monoclonal antibody.  Proc. Natl. Acad. Sci. (PNAS) 2000;(4);97:285-90.
  13. Gross DJ, Weiss L, Reibstein I, Hedlund G, Dalen E, Rapoport M, Slavin S.  The immunomodulator Linomide: Role in treatment and prevention of autoimmune diabetes mellitus.  International Immunopharmacology 12001:1131-1139.
  14. Elkin G, Prighozina T.B., Gurevitch O, Slavin S.  Non myeloablative bone marrow transplantation based on deletion of host-anti-donor alloreactive cells prevents autoimmune insulitis and diabetic mice.  Trans Proceedings 2002;34:1303-1306.
  1. Slavin S.  Successful treatment of autoimmune disease in (NZB/NZW)F1 female mice by using fractionated total lymphoid irradiation. Proc Natl Acad Sci USA 1979;76:5274-5276.
  2. Fuks Z, Slavin S.  The use of total lymphoid irradiation (TLI) as immunosuppressive therapy for organ allotransplantation and autoimmune diseases. Int J Rad Oncol Biol Phys 1981;7:79-82.
  3. Moscovitch M, Slavin S.  Regulation of the immune response in experimental models of autoimmune disorders. 1. Immunocompetence and transplantation tolerance in (NZB x NZW)F1 hybrid mice immunosuppressed with total lymphoid irradiation and in reconstituted bone marrow chimeras. J Clin Lab Immunol 1983;4:185-191.
  4. Moscovitch M, Slavin S.  Regulation of the immune response in experimental models of autoimmune disorders. 2. Induction of suppressor cells of the mixed lymphocyte culture in adult (NZB x NZW)F1 mice using total lymphoid irradiation. J Clin Lab Immunol 1983;11:67-74.
  5. Moscovitch M, Rosenmann E, Neeman Z, Slavin S.  Successful treatment of autoimmune manifestations in MRL/1 and MRL/n mice using total lymphoid irradiation (TLI). Exp Molec Pathol 1983;38:33-47.
  6. Slavin S.  The use of total lymphoid irradiation (TLI) for the treatment of autoimmune disorders. Is J Med Sci 1988; 24:375-8.
  7. Karussis DM, Slavin S, Ben-Nun A, Ovadia H, Vourka-Karussis U, Lehmann D, Mizrachi-Kol R, Abramsky O. Chronic-relapsing experimental autoimmune encephalomyelitis (CR-EAE): treatment and indution of tolerance, with high dose cyclophosphamide followed by syngeneic bone marrow transplantation. J Neuroimmunol 1992;39:201-210.
  8. Karussis DM, Slavin S, Lehmann D, Mizrachi-Koll R, Abramsky O, Ben-Nun A. Prevention of experimental autoimmune encephalomyelitis and induction of tolerance with acute immunosuppression followed by syngeneic bone marrow transplantation. J Immunol 1992;148:1693-1698.
  9. Slavin S.  Treatment of life threatening autoimmune diseases with myeloablative doses of immunosuppressive agents and autologous bone marrow transplantation – rationale and experimental background. BMT 1993;12:85-88.
  10. Slavin S, Karussis D, Weiss L, Vourka-Karussis U, Abramsky O. Immunohematopoietic reconstitution by allogeneic and autologous bone marrow grafts as a means for induction of specific unresponsiveness to donor-specific allografts and modified self in autoimmune disorders. Transplant Proc 1993;25:1274-1275.
  11. Karussis DM, Vourka-Karussis U, Lehmann D, Abramsky O, Ben-Nun A, Slavin S. Successful treatment of autoimmunity in MRL/lpr mice with T-cell depleted syngeneic bone marrow transplantation. EOS J Immunol Immunopharm 1993:XIII:78-79.
  12. Karussis DM,  Lehmann D, Slavin S, Vourka-Karussis U, Mizrachi-Koll R, Ovadia H, Ben-Nun A, Kalland T, Abramsky O. Inhibition of acute, experimental autoimmune encephalomyelitis by the synthetic immunomodulator Linomide, Ann. Neurol 1993 34:(5);654-660.
  13. Slavin S, Karussis DM, Weiss L, Karussis-Vourka U and Abramsky O. Induction of tolerance to allo and self-antigens with syngeneic bone marrow transplantation. Transpl. Proc. 1993;25:1274-1275.
  14. Karussis DM, Vourka-Karussis U, Lehmann D, Abramsky O, Ben-Nun A, Slavin S. Immunomodulation of autoimmunity in MRL/1pr mice with syngeneic bone marrow transplantation (SBMT). Clin Exp Immunol1995;100(1):111-117.
  15. Blank M, Tomer Y, Slavin S, Shoenfeld Y. Induction of tolerance to experimental anti-Phospholipid syndrome (APS) by syngeneic bone marrow cell transplantation.  Scand. J. Immunol 1995;42:226-234.
  16. Slavin S. Autologous and allogeneic stem cell transplantation for the treatment of autoimmune diseases as a potential new approach.   The Decade of Autoimmunity.  (Yehuda Shoenfeld, Editor)  Elsevier. 1999:399-408.
  17. Slavin S, Nagler A.  Bone marrow transplantation for cancer and autoimmunity.  Cancer and Autoimmunity. Editors, Y. Shoenfeld and Eric Gershwin. Elsevier, 2000:409-421.
  18. Slavin S, Nagler A, Varadi G, Or R. Graft vs autoimmunity following allogeneic non-myeloablative blood stem cell transplantation in a patient with chronic myelogenous leukemia and severe systemic psoriasis and psoriatic polyarthritis. Exp Hematol 2000 Jul;28(7):853-7.
  19. Richard K. Burt, Walter Barr, Yu Oyama, Ann Traynor, Shimon Slavin.  Future strategies in hematopoietic stem cell transplantation for rheumatoid arthritis. J of Rheumatology. 2001;28(64);42-48.
  20. Burt R.K, Slavin S, Burns W.H, Marmont A.M.  Induction of tolerance in autoimmune diseases by hematopoietic stem cell transplantation: Getting closer to a cure?    Blood, 2001;99(3)768-784.
  21. Slavin S, Paveletic S, Burt B.  Allogeneic hematopoietic stem cell transplantation of rheumatoid arthritis.  2002.
  22. Burt R.K, Slavin S, Burns W.H, Marmont A.M.  Induction of tolerance in autoimmune diseases by hematopoietic stem cell transplantation: Getting closer to a cure?  Int J of Hematology 2002;76 (Suppl 1):226-247. Also presented at the 29th World Congress of the International Society of Hematology (2002 Seoul ISH).  Seoul, Korea.  August 24th-28th, 2002.
  23. Burt KR, Verda L, Oyama Y, Statkute L, Slavin S.  Non-myeloablative stem cell transplantation for autoimmune diseases.  Springer Semin Immun (2004) 26:57–69.
  24. Slavin S, Marmont A, Burt R. Allogeneic hematopoietic stem cell transplantation for autoimmune disease. Stem Cell therapy for Autoimmune Disease.  Editors: Richard K. Burt & Alberto M. Marmont. Publishers: Landes Bioscience, Texas, USA. 2004:474-478.
  25. Burt RK, Verda L, Oyama Y, Statkute L, Slavin S.  Non-myeloablative stem cell transplantation for autoimmune diseases. Chapter in Seminars and Immunopathology. Publisher Springer, Heidelberg, Germany. 2004;26:57-69.
  26. Burt R, Cohen B, Rose J, Petersen F, Oyama Y, Stefoski D, Katsamakis G, Carrier E, Kozak T, Muraro PA, Martin R, Hintzen R, Slavin S, Karussis D, Haggiag S, Voltarelli JC, Ellison GW, Jovanovic B, Popap U, McGuirk J, Statkute L, Verda L, Haas J, Arnold R.  Hematopoietic stem cell transplantation for multiple sclerosis. Arch Neurol. 2005;62(6):860-864.