Clinical translation of stem cell based interventions for spinal cord injury — Are we there yet?

Chhabra, Harvinder Singh; Sarda, Kanchan

doi:10.1016/j.addr.2017.09.021

Cited by 52 publications

(61 citation statements)

References 87 publications

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“…73 Questions relating to the type of cells used, number, and safety remain to be addressed. 74 Stem cell therapy remains experimental and it cannot ethically be offered to patients as a proven form of treatment.…”

Section: Neuroregenerative and Neuroprotective Therapiesmentioning

confidence: 99%

“…On the contrary, delayed administration may result in no neuroregenerative effects because of the loss of cell plasticity at the site of injury and extensive scar and cyst formation. 74 Studies have suggested that cell transplantation during the subacute stage is more effective than that during acute or chronic stages. 1 Hence, in most previous studies, cells were administered during the subacute stage.…”

Section: Reproduced Withmentioning

confidence: 99%

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Regenerative Therapies for Spinal Cord Injury

Ashammakhi

Kim

Ehsanipour

et al. 2019

Tissue Engineering Part B: Reviews

121

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Spinal cord injury (SCI) is a serious problem that primarily affects younger and middle-aged adults at its onset. To date, no effective regenerative treatment has been developed. Over the last decade, researchers have made significant advances in stem cell technology, biomaterials, nanotechnology, and immune engineering, which may be applied as regenerative therapies for the spinal cord. Although the results of clinical trials using specific cell-based therapies have proven safe, their efficacy has not yet been demonstrated. The pathophysiology of SCI is multifaceted, complex and yet to be fully understood. Thus, combinatorial therapies that simultaneously leverage multiple approaches will likely be required to achieve satisfactory outcomes. Although combinations of biomaterials with pharmacologic agents or cells have been explored, few studies have combined these modalities in a systematic way. For most strategies, clinical translation will be facilitated by the use of minimally invasive therapies, which are the focus of this review. In addition, this review discusses previously explored therapies designed to promote neuroregeneration and neuroprotection after SCI, while highlighting present challenges and future directions.

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Section: Neuroregenerative and Neuroprotective Therapiesmentioning

confidence: 99%

Section: Reproduced Withmentioning

confidence: 99%

Regenerative Therapies for Spinal Cord Injury

Ashammakhi

Kim

Ehsanipour

et al. 2019

Tissue Engineering Part B: Reviews

121

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“…[1] The secondary injury is the major pathological process that aggravates the tissue damage and hinders the recovery, mainly by the heightened inflammation related damage. [2] Therapeutic agents have been investigated to counter the secondary injury, but the therapeutic effect is frequently limited by the poor accumulation, the short retention and the lack of controlled release of therapeutics in lesion tissue. [3] Owing to the poor tissue accumulation, a high drug dose is frequently required for most therapeutics with systemic administration, while severe systemic side effects followed with unstable efficacy has arouse a great controversy on this bolus treatment.…”

Section: Introductionmentioning

confidence: 99%

Scar Tissue‐Targeting Polymer Micelle for Spinal Cord Injury Treatment

Wang

Liang

et al. 2020

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Spinal cord injury (SCI) is a devastating disorder, leading to permanent motor and sensory deficit. Despite recent advances in neurosciences, the treatment efficacy on SCI patients remains unsatisfactory, mainly due to the poor accumulation, short retention, and lack of controlled release of therapeutics in lesion tissue. Herein, an injured spinal cord targeting prodrug polymer micelle is built. An esterase‐responsive bond is used to link apocynin (APO) monomer, because of the enhanced esterase activity found in microglia cells after activation, which ensures a controlled degradation of APO prodrug (Allyloxypolyethyleneglycol‐b‐poly [2‐(((4‐acetyl‐2‐methoxyphenoxy)carbonyl)oxy)ethyl methacrylate], APEG‐PAPO or PAPO) by activated microglia cells. A scar tissue‐homing peptide (cysteine‐alanine‐glutamine‐lysine, CAQK) is introduced to the PAPO to endow the polymer micelle the lesion tissue‐targeting ability. As a result, this CAQK‐modified prodrug micelle (cPAM) exhibits an improved accumulation and prolonged retention in lesion tissue compared to the control micelle. The cPAM also leads to superior tissue protection and sustained motor function recovery than the control groups in a mouse model of SCI. In conclusion, the cPAM induces an effective treatment of SCI by the lesion tissue specific delivery of the prodrug polymer via its robust scar binding effect, making the scar tissue a drug releasing platform for sustained treatment of SCI.

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“…Investigated cell types include Schwann cells, olfactory ensheathing cells, mesenchymal stem cells, neural stem and progenitor cells, and embryonic cell-derived or inducible pluripotent stem cell-derived neural precursor cells. 5 In our patient, olfactory mucosa was used as an autologous graft because it is readily accessible and contains neural stem and progenitor cells and olfactory ensheathing cells. 1 It is postulated that these cells maintain a lifelong capacity to differentiate into neurons and glia while also supporting axonal regrowth.…”

Section: Discussionmentioning

confidence: 99%