Neglected No More: Emerging Cellular Therapies in Traumatic Injury

Lowry, Lacy E.; Herzig, Maryanne C.; Christy, Barbara A.; Schäfer, Richard; Pati, Shibani; Andrew, P.; Bynum, James A.

doi:10.1007/s12015-020-10086-7

Cited by 4 publications

(5 citation statements)

References 251 publications

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“…After a severe traumatic injury, inflammation, edema, and dysregulated immune responses often cause damage secondary to the injury itself. The administration of human adult stem‐like or progenitor cells to modulate and dampen these damaging responses is the basis for multiple clinical trials 2 . However, the use of live cells in the clinic presents logistical challenges which are especially challenging in austere settings such as small community hospitals or forward military medical facilities.…”

Section: Discussionmentioning

confidence: 99%

“…The administration of human adult stem-like or progenitor cells to modulate and dampen these damaging responses is the basis for multiple clinical trials. 2 However, the use of live cells in the clinic presents logistical challenges which are especially challenging in austere settings such as small community hospitals or forward military medical facilities. Products need to be transported and stored easily; this need has increased the interest in cell-free products such as secretomes, EVs, or exosomes.…”

Section: Discussionmentioning

confidence: 99%

“…Cellular therapies have been considered for the treatment of traumatic injury [1][2][3][4] with mesenchymal stromal cells (MSCs) being the most common option. 2 MSCs can modulate immune responses, influence vascular permeability and angiogenesis, and dampen inflammation. 5,6 They are believed to be immune-privileged and safe for human intravenous administration.…”

Section: Introductionmentioning

confidence: 99%

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Refrigerated human mesenchymal stromal cells as an alternative to cryostorage for use in clinical investigation

et al. 2023

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Background Mesenchymal stromal cells (MSCs) and other therapeutic cells show efficacy for cardiac damage, neurological disease, chronic lung disease, pediatric graft versus host disease, and several inflammatory conditions. Based on their anti‐inflammatory and immune‐modulatory activities, responsiveness, and secretion of beneficial factors, cellular therapeutics may provide benefits in acute and chronic traumatic injury. However, the use of live cells presents logistical challenges, especially for military trauma. MSCs are generally shipped and stored frozen but require sterile handling before infusion. This requires skilled personnel and equipment not readily available in a forward medical treatment facility or even a small community hospital. Methods Commercial human bone marrow‐ and adipose‐derived MSCs from multiple donors were cultured under standard conditions, harvested and stored at 4°C in solution for up to 21 days. Cell viability, ATP content, apoptosis, proliferation capability, immunomodulation activity, and responsiveness were assessed after different amounts of time. Results Human MSCs can be stored at 4°C in MSC culture medium for 14 days while maintaining a reasonable level of viability and function. Both viability and function are reduced when MSCs are stored in crystalloid solutions. Conclusions This approach makes it feasible to prepare cellular therapeutic agents in a laboratory or commercial facility and ship them under refrigerated conditions. Once they reach their destination, they can be stored at 4°C under conditions similar to blood products. Cells prepared and stored this way could also be used directly with minimal handling, making them more practical for both civilian and military trauma.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Refrigerated human mesenchymal stromal cells as an alternative to cryostorage for use in clinical investigation

et al. 2023

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“…Major trauma is one of the leading causes of death and disability [ 1 , 2 ]. Typically, trauma patients are relatively young and the sustained injuries not only adversely affect health and wellbeing [ 3 ], but also result in a high number of disability-adjusted life years (DALYs) [ 4 – 6 ]. In addition to the human impact of traumatic injuries, their economic impact can also be substantial [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Barriers and facilitators associated with the upscaling of the Transmural Trauma Care Model: a qualitative study

Ratter,

Wiertsema,

Ettahiri

et al. 2024

BMC Health Serv Res

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Background To assess the barriers and facilitators associated with upscaling the Transmural Trauma Care Model (TTCM), a multidisciplinary and patient‐centred transmural rehabilitation care model. Methods Semi-structured interviews were conducted with eight trauma surgeons, eight hospital-based physiotherapists, eight trauma patients, and eight primary care physiotherapists who were part of a trauma rehabilitation network. Audio recordings of the interviews were made and transcribed verbatim. Data were analysed using a framework method based on the “constellation approach”. Identified barriers and facilitators were grouped into categories related to structure, culture, and practice. Results Various barriers and facilitators to upscaling were identified. Under structure, barriers and facilitators belonged to one of five themes: “financial structure”, “communication structure”, “physical structures and resources”, “rules and regulations”, and “organisation of the network”. Under culture, the five themes were “commitment”, “job satisfaction”, “acting as a team”, “quality and efficiency of care”, and “patients’ experience”. Under practice, the two themes were “practical issues at the outpatient clinic” and “knowledge gained”. Conclusion The success of upscaling the TTCM differed across hospitals and settings. The most important prerequisites for successfully upscaling the TTCM were adequate financial support and presence of “key actors” within an organisation who felt a sense of urgency for change and/or expected the intervention to increase their job satisfaction. Trial registration NL8163 The Netherlands National Trial Register, date of registration 16-11-2019.

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“…Twenty years ago the first experimental study assessing MSC protective effects in TBI was published 10 . Since then interest has grown, attracting many research groups worldwide 11 – 13 . Results are promising but are hampered by the wide variability of therapeutic effects.…”

Section: Introductionmentioning

confidence: 99%

Systematic review and meta-analysis of preclinical studies testing mesenchymal stromal cells for traumatic brain injury

et al. 2021

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Mesenchymal stromal cells (MSCs) are widely used in preclinical models of traumatic brain injury (TBI). Results are promising in terms of neurological improvement but are hampered by wide variability in treatment responses. We made a systematic review and meta-analysis: (1) to assess the quality of evidence for MSC treatment in TBI rodent models; (2) to determine the effect size of MSCs on sensorimotor function, cognitive function, and anatomical damage; (3) to identify MSC-related and protocol-related variables associated with greater efficacy; (4) to understand whether MSC manipulations boost therapeutic efficacy. The meta-analysis included 80 studies. After TBI, MSCs improved sensorimotor and cognitive deficits and reduced anatomical damage. Stratified meta-analysis on sensorimotor outcome showed similar efficacy for different MSC sources and for syngeneic or xenogenic transplants. Efficacy was greater when MSCs were delivered in the first-week post-injury, and when implanted directly into the lesion cavity. The greatest effect size was for cells embedded in matrices or for MSC-derivatives. MSC therapy is effective in preclinical TBI models, improving sensorimotor, cognitive, and anatomical outcomes, with large effect sizes. These findings support clinical studies in TBI.

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Neglected No More: Emerging Cellular Therapies in Traumatic Injury

Cited by 4 publications

References 251 publications

Refrigerated human mesenchymal stromal cells as an alternative to cryostorage for use in clinical investigation

Refrigerated human mesenchymal stromal cells as an alternative to cryostorage for use in clinical investigation

Barriers and facilitators associated with the upscaling of the Transmural Trauma Care Model: a qualitative study

Systematic review and meta-analysis of preclinical studies testing mesenchymal stromal cells for traumatic brain injury

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