Treating childhood traumatic brain injury with autologous stem cell therapy

ABSTRACT

Introduction: Neonatal traumatic brain injury (TBI) is a significant cause of developmental disorders. Autologous stem cell therapy may enhance neonatal brain plasticity towards repair of the injured neonatal brain.

Areas covered: The endogenous neonatal anti-inflammatory response can be enhanced through the delivery of anti-inflammatory agents. Stem cell therapy stands as a robust approach for sequestering the inflammation-induced cell death in the injured brain. Here, we discuss the use of umbilical cord blood cells and bone marrow stromal cells for acute and chronic treatment of experimental neonatal TBI. Autologous stem cell transplantation may dampen neuroinflammation. Clinical translation of this stem cell therapy will require identifying the therapeutic window post-injury and harvesting ample supply of transplantable autologous stem cells. Stem cell banking of cryopreserved cells may allow readily available transplantable cells and circumvent the unpredictable nature of neonatal TBI. Harnessing the anti-inflammatory properties of stem cells is key in combating the progressive neurodegeneration after the initial injury.

Expert opinion: Combination treatments, such as with hypothermia, may enhance the therapeutic effects of stem cells. Stem cell therapy has immense potential as a stand-alone or adjunctive therapy for treating neuroinflammation associated with neonatal TBI acutely and for preventing further progression of the injury.

KEYWORDS:

• Traumatic brain injury
• neuroinflammation
• neuroplasticity
• hypoxic ischemic encephalopathy
• neonatal
• stem cells
• umbilical cord blood cells
• bone marrow stromal cells
• autologous

Article highlights

• Neonatal traumatic brain injury is a debilitating disorder that has limited therapeutic options.

• Inflammation is a major pathological manifestation of the injured neonatal brain.

• Regenerative medicine via stem cell therapy offers a novel treatment for the injured neonatal brain.

• Autologous stem cell transplantation can sequester neuroinflammation, thereby reducing the secondary cell death damage associated with neonatal traumatic brain injury.

• Translation of stem cell therapy from the laboratory to the clinic will need to consider optimal cell dose, timing, and route of cell delivery.

• Enhanced therapeutic outcomes of cell therapy will likely be complemented by combination treatments, such as with hypothermia, altogether targeting the neuroinflammation-plagued neonatal traumatic brain injury.

This box summarizes key points contained in the article.

Declaration of interest

CV Borlongan has patent applications related to stem cell therapy with Athersys Inc., Saneron CCEL, and SanBio Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

CV Borlongan is funded by NIH NINDS R01NS071956-01, NIH NINDS R01NS090962, NIH NINDS R21NS089851-01, NIH NINDS R21094067, Veterans Affairs BX001407-01, NeuralStem, Karyopharm, SanBio Inc., International Stem Cell Corp., Saneron CCEL.