Несмотря на наличие антибиотиков, вакцин и др., проблема лечения хронической инфекции остается актуальной. Лично я не верю в феномен иммунного истощения, думаю, что там имеют место иные механизмы. Думаю, что интересно обсудить использование стволовых клеток при хронических инфекциях. Литература по этому вопросу имеется и довольно обширная.

Вопрос о применении стволовых клеток при хронических инфекциях представляет не мой взгяд большой теоретический интерес(не говоря о практическом). Напоминаю, что атеросклероз также по современным взглядам представляет собой хроническую инфекцию. Но нет смысла рассматривать здесь аутоиммунные аспекты проблемы(для этого был специальный топик). Здесь есть смысл обсудить могут ли стволовые клетки справиться с иммунной недостаточнстью и с разрушением тканей, сопровождающих хроническое инфекционное воспаление воспаление.

Iguchi A, Kobayashi R, Sato TZ, Nakajima M, Kaneda M, Ariga T. Successful report of reduced-intensity stem cell transplantation from unrelated umbilical cord blood in a girl with chronic active Epstein-Barr virus infection. J Pediatr Hematol Oncol. 2006 Apr;28(4):254-6.

We describe an 8-year-old girl with chronic active Epstein-Barr virus (EBV) infection (CAEBV) who was treated successfully by reduced-intensity stem cell transplantation (RIST) from unrelated cord blood (CB). She had been suffering from fever, abdominal pain, and interstitial lymphadenopathy, and CAEBV was
diagnosed. After chemotherapy that included etoposide, the amount of EBV decreased transiently below the detection level. However, the disease due to CAEBV worsened despite the chemotherapy, and she finally needed chemotherapy every week. Therefore, instead of conventional myeloablative transplantation, we performed CB transplantation with reduced-intensity conditioning regimens
consisting of low-dose total body irradiation, fludarabine, and etoposide. CB, for which human leukocyte antigen (HLA) was 2-loci mismatched on the DR loci from an unrelated donor, was infused after conditioning. Although grade III acute graft-versus-host disease (GVHD) in the gut and chronic GVHD in the lung developed, the symptoms of GVHD disappeared with immunosuppressive therapy.
After 15 months, the patient remained a complete chimera, with undetectable levels of EBV in peripheral blood and bone marrow. We conclude that RIST from unrelated CB can be indicated for some cases of CAEBV who are refractory to chemotherapy and have no HLA-matched related and unrelated donors as the source of bone marrow or peripheral blood stem cells.

Ross JJ. Angiogenic gene therapy as a potential therapeutic agent in chronic osteomyelitis. Med Hypotheses. 2006;67(1):161-3. Epub 2006 Mar 7.

Bacterial osteomyelitis is common, and outcomes are often poor. Standard therapies fail in 31% of cases, and lower extremity amputation and loss of independent functional status are common. Innovative therapies are desperately needed, particularly in diabetic patients with peripheral vascular disease at
high risk for bad outcomes. Angiogenic gene therapy is a novel, logical and promising approach in these patients. Adult bone is not well vascularized. Host inflammation and bacterial toxin production result in further loss of vascularity, and produce bone necrosis. Dead bone acts as a foreign body, and is
permissive for persistent infection. Poor blood supply prevents remodeling of dead bone, delivery of antibiotics, and phagocytosis of bacteria. Therefore, angiogenic gene therapy may be a useful therapeutic agent in osteomyelitis. It is reasonable to pursue studies of angiogenic agents in established animal
models of chronic osteomyelitis, not only with vascular endothelial growth factor (VEGF), but also with the powerful bone angiogenic agent, placental growth factor, as well as other agents with tissue regenerative and angiogenic potential, such as sonic hedgehog, bone morphogenetic proteins, matrix metalloproteinase-9, secretoneurin, and perhaps pluripotent stem cells. If successful, animal studies could lead to pilot studies of one or more of these agents as adjunctive therapy, in addition to antibiotics, in diabetic patients with chronic osteomyelitis who have failed conventional treatment.
Sergo2

Я посмотрел литературу по теме immune deficiency and stem cells. Много литературы по применению стволовых клеток при лечении первичных иммунодефицитов, но есть и при лечении вторичных иммунодефицитов, которые имеют место при хронических инфекциях.
Я удивляюсь отсутствию активности участников Форума в данной теме. Неужели не интересно, как можно применять стволовые клетки, например, при СПИДе? Тем более, что я знаю, что среди участников Форума много людей, разбирающихся в вопросах иммунологии на самом высоком уровне.

Kohn DB. Gene therapy for hematopoietic and immune disorders. Bone Marrow Transplant. 1996 Dec;18 Suppl 3:S55-8.
Gene therapy is a novel approach under investigation for the treatment of genetic diseases, cancer and AIDS. Hematopoietic stem cells would be the target cell for correction of hemoglobinopathies, immune deficiencies and lysosomal storage diseases. Retroviral vectors derived from murine leukemia viruses have been used most extensively for gene delivery, but are limited in their capacity to transduce pluripotent human hematopoietic stem cells. In a trial of gene transfer for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID), three neonates were treated with infusion of autologous umbilical cord blood CC34+ cells. Up to 3 years later, a low number of leukocytes are still being produced containing the inserted ADA gene, with evidence of selective accumulation of transduced T lymphocytes. Further successful applications of gene therapy will require development of more
efficient methods of gene transfer into stem cells.

Kohn DB. Gene therapy for hematopoietic and immune disorders.


Gene therapy is a novel approach under investigation for the treatment of genetic diseases, cancer and AIDS. Hematopoietic stem cells would be the target cell for correction of hemoglobinopathies, immune deficiencies and lysosomal storage diseases. Retroviral vectors derived from murine leukemia viruses have been used most extensively for gene delivery, but are limited in their capacity to transduce pluripotent human hematopoietic stem cells. In a trial of gene transfer for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID), three neonates were treated with infusion of autologous umbilical cord blood CC34+ cells. Up to 3 years later, a low number of leukocytes are still being produced containing the inserted ADA gene, with evidence of selective accumulation of transduced T lymphocytes. Further successful applications of gene therapy will require development of more
efficient methods of gene transfer into stem cells.
Sergo2

В принципе стволовые клетки можно при менять при следующих патологических поцессах. Наследственные и врожденные аномалии, травмы, аутоимунные заболевания, инфекции. Список получился не очень длинным. Каждая позиция имеет свою специфику.

http://newsroom.ucla.edu/page.asp?RelNum=7166

О иммунодефицитах при хронических инфекциях.
McGavern DB. Immunotherapeutic relief from persistent infections and amyloid disorders.
Neurology. 2006 Jan 24;66(2 Suppl 1):S59-64.
Persistent infections and amyloid disorders afflict a significant number of people worldwide. It would appear at first glance that the treatment of these afflictions should be entirely unrelated; however, in both cases components of the adaptive immune system have been harnessed in an attempt to provide some
therapeutic relief. Given that the ability of a pathogen to establish persistence often depends in part on a shortcoming of the adaptive immune response, it seems logical to devise immunotherapies with the intention of supplementing (or replacing) the insufficient immunologic element. A case in point is an intervention referred as immunocytotherapy, which relies upon the adoptive transfer of pathogen-specific T lymphocytes into a persistently infected host. Remarkably, the adoptively transferred T lymphocytes not only have the capacity to clear the persistent infection, but can also provide the recipient with protection against subsequent rechallenge (i.e., immunologic memory). Treatment of amyloid disorders (e.g., Alzheimer disease, sporadic inclusion-body myositis) with a similar therapeutic approach is complicated by the fact that the aberrant protein accumulations are self-derived. Focusing the adaptive response on these aberrant self-proteins has the potential to result in autoimmune pathology. This review critically evaluates the importance of immunotherapeutic approaches for the treatment of persistent infections and
amyloid disorders, and attempts to delineate the interventions that are most likely to succeed in an exceedingly complex disorder such as sporadic inclusion-body myositis.

К своему удивлению я обнаружил, что трансплантация костного мозга не только практически не используется прри хронических инфекциях, но наоборот аллогенаая трансплантация костного мозга иногда ведет к возникновению инфекций.