Developments in intracerebral stem cell grafts

Abstract

The field of stem cell therapy has emerged as a promising research area for brain repair. Optimizing the safety and efficacy of the therapy for clinical trials will require revisiting transplantation protocols. The cell delivery route stands as a key translational item that warrants careful consideration in facilitating the success of stem cell therapy in the clinic. Intracerebral administration, compared to peripheral route, requires an invasive procedure to directly implant stem cells into injured brain. Although invasive, intracerebral transplantation circumvents the prohibitive blood brain barrier in allowing grafted cells when delivered peripherally to penetrate the brain and reach the discreet damaged brain tissues. This review will highlight milestone discoveries in cell therapy for neurological disorders, with emphasis on intracerebral transplantation in relevant animal models and provide insights necessary to optimize the safety and efficacy of cell therapy for the treatment of Parkinson’s disease, Huntington’s disease, stroke, and traumatic brain injury.

Treating childhood traumatic brain injury with autologous stem cell therapy

“…UCBCs show potential in treating neonatal TBI cases because they can be easily transplanted through autologous means (reducing the possibility of infection or rejection) are readily available, and often have a high proliferative capacity [27]. While the proliferative capacity of stem cells is part of what makes them attractive treatment options, this property can also become tumorigenic if left unregulated [28]. Because neurons and connectivity continues to worsen after the acute-phase, treatment during the acute phase of injury has the potential to better the outcome of individuals afflicted with HIE.…”

“…Stem cells have been injected intravenously, directly into brain regions (i.e. intracerebral), or intra-arterially [28], and each injection route comes with advantages and disadvantages: intravenous injections are not very invasive but may be unable to surpass the BBB, intra-arterial injections is more invasive but has a higher probability of mobilizing cells across the BBB, while intracerebral injections display the highest degree of cell engraftment but are by far the most invasive. The anti-inflammatory effects seen with peripheral injections are likely due to the systemic dispersion of anti-inflammatory molecules that are not able to penetrate intact BBBs [35, 42–43].…”

Mesenchymal stem cell-based therapy for ischemic stroke

“…The minimally invasive intravenous or intra-arterial delivery of stem cells has been the preferred choice for the subacute phase due to an already injured brain produced by the primary ischemic insult, combined with chemoattractants that can guide migration of MSCs from the periphery to the brain. The direct intracerebral implantation of stem cells to the peri-infarct region is utilized for the chronic phase with the stroke brain more tolerant of an invasive treatment procedure, but also because of tapered levels of chemoattractants [62]. Direct transplantation was initially examined in chronic stroke patients using neural progenitor cells (NT2N) [63] and in recent years using Notch-induced bone marrow cells (SB-623) [64], with subsequent clinical trials employing intravenous and intra-arterial administration of MSCs in subacute stroke patients [65,66].…”

Translational lab-to-clinic hurdles in stem cell therapy

“…However, the intracerebral (IC) approach is the ideal method of administration for chronic stroke patients because the chemokine signal is not as strong as the early stage [21]. Several factors must be considered in determining the choice of stem cell transplant route.…”