Mesenchymal Stem Cells Derived from Human Umbilical Cord Attenuate the Mortality Rate of Experimentally Induced Heatstroke

人類臍帶間質幹細胞降低小鼠因熱中風所引發的死亡率

熱中風為臨床醫學上一種危急的疾病，主要症狀有高熱、低血壓、肝腎衰竭、血管凝血病變、全身性發炎、大腦缺血損傷以及功能失調。由我們先前實驗得知人類臍帶血造血幹細胞(hUCBHSCs)可復甦改善熱中風大鼠。而人類臍帶間質幹細胞(hUCMSCs)乃是由臍帶上Wharton’s jelly所純化出高潛能的細胞。和人類骨髓間質幹細胞相較，hUCMSCs有細胞數量充足、無痛收集、無捐贈者併發症及在體外有著快速而長時間的自我增生的優勢。因此，本研究主要探討hUCMSCs改善小鼠因熱中風所引發的死亡率。藉由hUCMSCs治療於小鼠的熱中風模式，探討是否能降低多功能器官失調而達到延長存活時間或比率。實驗動物為八週齡ICR雄性小鼠，隨機分三組別，包括：常溫控制組、熱中風控制組、熱中風治療組。除常溫對照組小鼠置於室溫環境未受熱外，其餘小鼠均給予「全身性均勻受熱」的動物模式，維持41.5℃環境1小時，再取出置於室溫環境下，連續觀察四天存活者做為存活率的計算。同時，我們將利用免疫組織化學染色評估細胞損傷以及凋亡的情況。實驗結果顯示：經由hUCMSCs治療的熱中風小鼠，均能顯著性(1)降低熱中風引起的死亡率(2)降低腦神經細胞損傷(3)減少下視丘細胞凋亡現象。綜合上述結論，hUCMSCs治療作用可以保護熱中風引起的腦神經細胞損傷、與致命性傷害。

Heatstroke is a lethal disease characterized by hyperpyrexia. Hypotension, hepatic and renal failure, entering a hypercoagulable state, systemic inflammation and cerebral ischemia, and all the injury and dysfunction accompanying these conditions. Our previous study [Do you mean in a paper you published earlier? If you mean the present research, say so, and not “previous”] showed that human umbilical cord blood cells (hUCBC) derived from hematopoietic stem cell (hUCBHSC) transplantation can resuscitate rats in which heatstroke had been experimentally induced. Although it has been shown that mesenchymal stem cells derived from human umbilical cord can be used to rescue mice from potentially lethal heatstroke, the hypothesis here proposed is that it also improves survival during heatstroke by attenuating multiorgan dysfunction. The experimental animals consist of male, 8-wk-old ICR mice. The animals were randomly divided into three groups: a normothermic control group, a Saline vehicle-treated heaststroke group, and a hUCMSC vehicle-treated heaststroke group. The normothermic control group were left at room temperature. The other two groups were subjected to the animal heatstroke model of whole body hyperthermia (WBH) at 41.5℃ for 1 hour and then allowed to recover at room temperature. Mice that survived 4 days of WBH were classified as survivors. Concurrently with this research, immunohistochemical staining was employed to assess cell damage and apoptosis. It was expected that hUCMSCs would attenuates heatstroke mortality. The main results show that hUCMSC vehicle-treated mice all had significantly (1)attenuated heatstroke-induced mortality, (2)diminished neuronal brain damage, and (3)reduced numbers of apoptotic cells in the hypothalamus. In conclusion, MSCs can protect the mice from heatstroke-induced neuronal brain damage and attenuatee their mortality rate.