脐带与脐带血共同移植 治疗急性放射综合症
急性放射综合症(Acute Radiation Syndrome, ARS)是指短时间受到大量辐射所造成的严重疾病，病患初期会发生恶心、呕吐、腹泻、食欲不振、疲劳、发烧、甚至癫痫和昏迷等严重症状，并伴随皮肤损伤包括红肿和骚痒。1940年广岛和长崎的原子弹事件，以及1980年车诺比辐射外泄事件，许多生还者和消防人员都患有ARS。
ARS的病患若持续接触高剂量辐射，则会在数个月内死亡。死亡的原因为骨髓受到破坏，造成血液细胞生成不良，导致免疫功能低下与器官衰竭，最后因感染而造成死亡。如果没有死亡，也可能在数年后并发白血病、淋巴癌等血液恶性疾病。
科学家发现，间叶干细胞具备一些特性，可以用来治疗ARS。间叶干细胞可以分泌抗发炎激素(TGF-β、IDO、HGF)、血管生成因子(VEGF、Ang、bFGF)和造血生长因子，因此能减缓因辐射造成的发炎现象，并促进细胞与组织的修复。日前已在动物实验证实间叶干细胞对ARS的疗效，美国一家生技公司--Osiris Therapeutics获得政府的补助，即将进行人体试验。
脐带血含丰富的造血干细胞，能直接帮助ARS病患的血液再造，而间叶干细胞又具有辅助造血干细胞的植入，以及免疫调节的功能，与脐带血共同移植，能立即给于ARS病患细胞的治疗，并防止移植后抗宿主疾病(GVHD)。后期移植间叶干细胞，能继续达到抗发炎与组织修复的疗效，是未来治疗ARS的目标。此篇文章刊登在药物发现与发展杂志(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.