Name of journal: World Journal of Transplantation esps manuscript no: 18452 Manuscript Type: Original Article Retrospective Study

INTRODUCTION

A global incidence rate of traumatic spinal cord injury (SCI) is estimated as 23 cases per million^[1]. Regional incidence rates vary from 15 (Australia) to 40 (United States) cases per 1 million of population^[1]. The average age at injury increased from 28.7 years in the 1970s to 42.6 years since 2010^[2], still, the incidence of traumatic SCI peaks in young people^[1,3].

Although spinal fractures constitute only 0.44% of all injury types, the percentage of spinal traumas has dramatically increased (over 200-fold) for the past 7 decades. The analysis predicted 800 of new spinal cord injuries (SCI) per 10 million of population.

For the past two decades the therapeutic advances hold a lot of promise for the patients with SCI, but none of the available therapies led to restoration of the morphological structure of spinal cord and its functions. Various therapeutic programs improve outcomes and life quality of the injured only in a few cases, but still they remain unable to repair severe neurologic deficit and restore lost functions. Surgical approaches to repair SCI are aimed at orthopedic restoration of vertebral canal anatomy, and their results remain controversial. To date, an SCI is a final verdict that entails impossibility to return to the previous way of life, to restore previous working capacity and reproductive functions, resulting in tremendous social and economic losses. The total direct costs of SCI in the United States alone are estimated at about 7.7 billion USD^[4].

Inefficiency of the available SCI therapies was used to be explained by the absence of regeneration potential of adult neurons, and the opportunity to restore damaged neural cells has only recently been proved^[5]. By now, the first steps to develop new neurorestorational therapy of SCI have been made^[6,7], although no universally acknowledged methods to restore the spinal cord after the injury are observed. Novel cell techniques and tissue engineering methods can provide the solution; so, according to the Stem Cell Summit (2009) data, 34 million of patients received transplantations of stem cells of various origin, and 1 million of them were SCI patients^[8]. However, outcomes and long-term consequences of such transplantations remain as yet unknown.

The available experience is minimally documented and rather obscure, due to insufficient theoretical and experimental evidence of cell technologies, as well as underdeveloped methods of their application, when the fate of transplanted cells, their further differentiation and transformation are unclear. The crucial question of cancer development, triggered by the transplantation of stem cells, also remains unanswered. The myths and fears of possible negative consequences of stem cell therapy significantly interfere with the research and progress in the area.

We have transplanted cells for SCI for 25 years both in research and in clinical practice and have accumulated substantial experience of victories and defeats administrating allogeneic and xenogeneic fetal neural and mesenchymal cells, isolated from animal and human embryos of 10-24 gestation weeks, as well as embryonic stem neural cells, obtained from human blastocyst. This experience is summed up in our book^[9], and to date, we have refused from the clinical application of allogeneic and xenogeneic cell material for SCI. We believe the future of the SCI therapy to belong to the suspensions, prepared from autologous stem and progenitor cells, as under the SCI condition the organism specifies and individually tailors the cells for the treatment of their own SCI, along with the advantage of null immunologic and transplantation side effects and absence of undesirable paramedical ethic, legal and religious aspects^[10]. The only option to use the allogeneic stem cells for SCI is haploidentical stem cells or those of close relatives, and only after the HLA typing.

In the present article we would like to determine the basic parameters for the beginning of the cell therapy for SCI and the criteria to terminate it in clinical practice.