Ann Thorac Surg 2007;83:1490
© 2007 The Society of Thoracic Surgeons
Original Articles: Cardiovascular
Invited commentary
Tatu Juvonen, MD, PhD,
Petri Lehenkari, MD, PhD
Department of Cardiothoracic Surgery, Oulu University Hospital, PO Box 21, Oulu OYS, 90029 Finland
(Email: tatu.juvonen{at}oulu.fi; petri.lehenkari{at}oulu.fi).
Shi and colleagues [1] have presented an interesting and novel approach to modulate the ischemia-injury response in the spinal cord by introducing mesenchymal stem cells (MSCs) intrathecally. The authors show a significant improvement in spinal cord recovery after acute and subacute injection of MSCs before and at 24 hours, but not later than at 48 hours. The result they provide is based on an experimental procedure in which cells are isolated from the same breed, but not exactly from the same individuals, to which spinal cord damage is introduced using subrenal clamping.
The MSCs are capable of invading damaged tissue and indeed they show several characteristics common to tumor cells. The MSCs most likely participate in tissue repair directly by differentiation and in situ repair of the damaged tissue, and also by modulating the acute inflammatory response to injury. This modulation of the paracrine environment of the damaged site might explain the rather interesting finding by Shi and colleagues [1]. It seems that contrary to the brain, the spinal cord is rather deficient in many damage limiting mechanisms, such as angiogenesis, neurogenesis, synaptogenesis, and reduction and control of apoptosis. Indeed, as earlier data has shown, the reperfusion of the spinal cord as such seems to promote the necrosis of neurons at the infarction site.
The ability of MSCs to reduce the neuron damage after acute injection suggests that their presence might delineate this reperfusion damage. The MSCs also actively participate and integrate into the healing occurring at the damaged site. This finding is interesting and rises expectations for the therapeutic use of MSCs in a rather straightforward manner, by intrathecal injection. However, some questions still remain. First, cells were cultured and passaged to achieve an appropriate number of cells. In myocardial repair, the MSCs are introduced in mixture with other bone marrow mononuclear cells (BMCs). Would the BMCs be able to have a similar effect? Or is the reported efficacy bound to homogeneity of cell population, which can be achieved only after the appropriate culture period and conditions? Also, an intriguing question that remains is the mode of injury. Could the observed therapeutic effect and its limitations be due to ischemia-reperfusion damage and hence not applicable as such to other damage, such as spinal contusion? These remaining questions do not diminish the scientific value of this interesting article, which leads us all to think of nature’s course in tissue healing and our means to guide these processes using cellular therapies.
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References
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- Shi E, Kazui T, Jiang X, et al. Therapeutic benefit of intrathecal injection of marrow stromal cells on ischemia-injured spinal cord Ann Thorac Surg 2007;83:1484-1490.[Abstract/Free Full Text]
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