Injection Time-Dependent Effect of Adult Human Bone Marrow Stromal Cell Transplantation in a Rat Model of Severe Traumatic Brain Injury

Abstract

The object of this study is to evaluate the effects of injecting adult human bone marrow stromal cells (hBMSCs) into rats with severe traumatic brain injury in acute phase and to determine more optimal injection timing between day 1 and day 2 postinjury. The lateral fluid percussion injury model was used. Adult hBMSCs were transplanted into hemisphere to injury sites in the corpus callosum ipsilateral on day 1 (n = 12) or day 7 (n = 8) after injury. A control group (n = 7) underwent only a sham operation without stem cell transplantation. Rats in all groups were analyzed by magnetic resonance spectroscopy (MRS), and by using behavioral, rotarod, and Barnes maze tests on day 1, 7, 14, and 42. Another nine randomly designated rats were sacrificed for immunohistochemical staining. Behavioral test scores increased significantly at all time-points after TBI in the day 7-injected group, compared to the others (p=0.008). GFAP staining was lower on day 42 in day 7-injected rats than in those injected on day 1. But no significant inter- or intra-group differences were observed for other tests. The injection of hBMSCs was found to have limited therapeutic potential with respect to neuroprotection after traumatic brain injury. However, because injection on day 7 after TBI produced greater functional improvements in neurobehavioral tests and more effectively suppressed astroglial activation than an injection on post-injury day 1, we cautiously recommend the injection time of day 7 post injury in hBMSCs transplantation in severe TBI, rather than day 1 post injury but further studies on developing hBMSC-based new therapeutic approaches should be warranted for improving neuroprotection in severe TBI.

Preclinical progenitor cell therapy in traumatic brain injury: a meta-analysis

“…Thirty-eight studies met inclusion criteria and underwent data extraction and quality assessment. Of these studies, some reported more than one pertinent outcome measure so that a total of 10 studies presented data for RR outcomes (16–25), 14 presented data on LV outcomes (23, 26–38), 21 assessed NSS outcomes (17–21, 23–26, 28, 29, 31, 36, 38–53), and 13 presented data on MWM testing (17, 18, 24, 26, 28, 29, 36, 38, 49–53). Specific study characteristics are listed in Table 1.…”

“…There are few, if any, chronic diseases in medicine that are treated with a single dose of medication. Though four included papers in our analysis looked at multiple doses (16, 23, 31, 52), this is not currently standard in the pre-clinical or the clinical literature. Future directions may include multiple doses for a greater and longer-lasting effect.…”

Effects of bone marrow mesenchymal stromal cells-derived therapies for experimental traumatic brain injury： A meta-analysis

“…1 ). An overall total of 55 studies were included in the meta-analysis) [ [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] , [74] , [75] , [76] , [77] ].

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“…Our results found that MSC(M) and MSC(M) derived EVs administered in TBI 24 h had better neurobehavioral outcomes than those injected greater than 24 h after TBI induction. Han et al found improvements in histological appearance and functional performance after treatment with human MSC(M) seven days after the injury instead of one day after the injury [ 39 ]. However, in human subjects, according to Tian et al there is an advantage of transplanting MSC(M) after a TBI in the window of efficacy that is most likely to result in the best results [ 90 ].…”

Stem cell therapy for acute cerebral injury

“…[52] Interestingly, stroke and TBI might have different optimal timing patterns. Studies in experimental stroke suggest there is greater functional recovery from mesenschymal stem cell and NSC transplantation at 24 hours compared to 7 days after stroke[53,54], with opposite results in experimental TBI[55]. …”