急性放射綜合症(Acute Radiation Syndrome, ARS)是指短時間受到大量輻射所造成的嚴重疾病，病患初期會發生噁心、嘔吐、腹瀉、食慾不振、疲勞、發燒、甚至癲癇和昏迷等嚴重症狀，並伴隨皮膚損傷包括紅腫和騷癢。1940年廣島和長崎的原子彈事件，以及1980年車諾比輻射外洩事件，許多生還者和消防人員都患有ARS。
ARS的病患若持續接觸高劑量輻射，則會在數個月內死亡。死亡的原因為骨髓受到破壞，造成血液細胞生成不良，導致免疫功能低下與器官衰竭，最後因感染而造成死亡。如果沒有死亡，也可能在數年後併發白血病、淋巴癌等血液惡性疾病。
科學家發現，間葉幹細胞具備一些特性，可以用來治療ARS。間葉幹細胞可以分泌抗發炎激素(TGF-β、IDO、HGF)、血管生成因子(VEGF、Ang、bFGF)和造血生長因子，因此能減緩因輻射造成的發炎現象，並促進細胞與組織的修復。日前已在動物實驗證實間葉幹細胞對ARS的療效，美國一家生技公司--Osiris Therapeutics獲得政府的補助，即將進行人體試驗。
臍帶血含豐富的造血幹細胞，能直接幫助ARS病患的血液再造，而間葉幹細胞又具有輔助造血幹細胞的植入，以及免疫調節的功能，與臍帶血共同移植，能立即給於ARS病患細胞的治療，並防止移植後抗宿主疾病(GVHD)。後期移植間葉幹細胞，能繼續達到抗發炎與組織修復的療效，是未來治療ARS的目標。此篇文章刊登在藥物發現與發展雜誌(Drug discovery & development)上。
Treating Acute Radiation Sickness with Mesenchymal Stromal Stem Cells
The recent nuclear crisis in Japan has highlighted the urgent need to develop products for the treatment of acute radiation sickness (ARS) and radiation exposure. Acute radiation sickness (ARS)—also known as radiation poisoning—occurs after accidental radiologic or nuclear exposure to a high dose of radiation over a short period of time.
Depending on the level of exposure, bone marrow aplasia may be combined with gastrointestinal (GI) involvement, cutaneous burns, muscle radiolysis, lung injury, and/or central nervous system failure, among other conditions. The prodromal phase consists of GI symptoms that include abdominal pain, nausea, vomiting, and diarrhea lasting an average of five days. During the latent phase, which occurs over the ensuing several days, the patient appears to be recovering. However, over the next several days to weeks, patients suffer a hematopoietic crisis from the depletion of erythropoietic, thrombocytopoietic, and leukopoietic precursors within the bone marrow. The illness phase is characterized by immunosuppression and multiple organ failure with death occurring within months following the initial exposure, usually from infection. Hematological malignancies, such as leukemia, can also occur years after exposure.
Based on these characteristics, mesenchymal stromal cells (MSCs)would, therefore, seem to be likely candidates as therapeutics for ARS. MSCs have been shown to be immune-privileged without the need for HLA matching even after repeat injections and have been documented to home specifically to radiation-injured tissues. In addition to reducing apoptosis, MSCs have been shown to secrete an abundance of therapeutic proteins, including anti-inflammatory and angiogenic cytokines and hematopoietic growth factors that are involved in the prevention and treatment of ARS by the reduction of inflammation and the support of angiogenesis. Additionally, MSCs have also been shown to promote hematopoietic recovery after lethal irradiation exposure.
With these attributes, it is no surprise that MSCs have proved to be effective in animal studies of ARS2, leading to governmental funding to expand the research and development of MSCs for this indication. One of the more recently discovered sources of MSCs that seems to be highly appropriate is the placenta. The placenta is essentially medical waste with a ubiquitous supply. Moreover, placental cells can be easily and inexpensively expanded ex vivo, and be made available as an allogeneic “off-the-shelf” product.
As with bone marrow-derived MSCs, placental-derived MSCs have been shown to possess favorable hypo-immunogenic properties, act via the secretion of anti-inflammatory and angiogenic factors, and potentially provide greater healing powers than older tissue sources. While ARS animal trials are still ongoing, early results have demonstrated that placental-derived MSCs enhance the engraftment of hematopoietic stem cells (HSCs) contained in cord blood when the MSCs and cord blood are administered concurrently. This would allow ARS patients to obtain cells for therapy immediately after exposure, as well as potentially use cells along with cord blood at a later date to repopulate the bone marrow if necessary.
