1 Introduction After sustaining a devastating spinal cord injury (SCI) and becoming paralyzed,a victim’s first concern is when he or she will again be able to stand and walk. More often than not,such miracles do not occur,and the individual succumbs to despair. Some science enthusiasts claim that they can help victims to walk again without defining exactly what type of walking is involved (e.g.,assisted or non‐assisted). Use of the arms to propel the trunk forward or using gravity to lean the trunk forward followed by passive forward swinging or sliding of the feet via momentum should not be defined as proper walking,as all such forward trunk movements are passive and occur largely as a result of gravitational forces. Moreover,merely walking is not sufficient to lead a relatively independent life. Rather,the victim must also maintain trunk stability and his or her hand or hands must be useful.

This article aims to discuss (1) the minimum power required for key muscles to ensure trunk stability; (2) the minimum power required for key muscles to facilitate walking in a paraplegic individual; and (3) the minimum power is required for key muscles to ensure hand usefulness or functionality. Although these points represent long‐standing knowledge,the precise relevance of these issues with regard to basic function has not been fully discussed. Therefore,a gap in knowledge remains with regard to the translation of neurological recovery to functional performance. Herein,knowledge about neurological recovery and biomechanics of the musculoskeletal system complement each other. This is important because once armed with knowledge about the musculoskeletal system,neuroscientists will understand the minimum possible and necessary achievements in neural recovery required to stabilize the trunk and ensure limb functionality. It might be a waste of time to expect the achievement of unachievable targets in the near future at our current scientific level,and thus we might deprive patients of benefits that they can already enjoy. Without an understanding of functional musculoskeletal system recovery,the translation of knowledge concerning neurological functions from the laboratory to bedside is incomplete. Despite obvious early sensory recovery after olfactory‐ensheathing cell transplantation,patients always expect motor recovery^[1]. Therefore,this article focuses only on motor functions. It is intended to fill a gap and complete the translation of knowledge concerning motor recovery (Figure 1).

2 Minimum requirements for musculoskeletal system functionality 2.1 Stability of the trunk The minimum power required for key muscle functioning should be achieved in order to stabilize the trunk. Otherwise,spinal instability will increase the difficulty experienced by the paraplegic in using his or her limbs efficiently and effectively,as the center of gravity would shift constantly in an unstable body. Severe instability might render walking and proper use of the upper limbs virtually impossible. The key muscle that contributes to minimal trunk stability is the latissimus dorsi (Figure 2). This muscle is innervated by spinal cord segments C6-8 but physically covers a vast area from the arms to the pelvis (two thirds of the back),far below the expected level of innervation for a cervical muscle. When the lower part of the trunk is paralyzed below the C8 level,powerful bilateral contractions of this muscle can maintain relative trunk stability. For this reason,the latissimus dorsi is nicknamed the “bridge muscle”^{[2, 3]}. It accordingly bridges the upper and lower parts of the body. However,this article does not aim to provide detailed descriptions of muscle‐strengthening exercises. In most humans,the center of gravity of the entire body is located immediately in front of the first or second segment of the sacrum while in a normal upright standing position (Figure 3)^[4]. When both feet are firmly on the ground,the body is stable because the center of gravity normally falls well within the margins of the base of support: the feet.

2.2 Walking What is the minimum power required for key muscles to facilitate walking in a paraplegic individual? Gait is an extremely complex mechanism that simultaneously ensures mobility and stability of the entire body. However,even scientific reports of the recovery of a paraplegic toward walking too often vaguely use the simple words “walk” and “walking” without defining the exact meanings. These definitions require urgent clarification to avoid confusing readers,particularly those without knowledge of the biomechanics of human gait (Figure 4) and who only read the title. In Phases b and e in Figure 4,the person stands on one foot. This is known as the Stance Phase. The other leg is bent backward to gain momentum before swinging forward to positions c and f in Figure 4,respectively. This is the Swing Phase. Next,the heel of the foot that has swung forward drops and touches the ground. It must roll over to allow the body to move forward together with its center of gravity. This is called the Rollover Phase from c to d and from f to g in Figure 4 for the other leg. The cycles of both legs end here,and the next cycles start again from b in Figure 4.

As seen in Figure 4,walking depends upon interchangeably lifting and moving the legs forward. It is different from sliding,during which both feet are on the ground at all times. It is also different from running,during which both feet leave the ground during one phase of the cycle. In a normal individual, the center of gravity of the body falls between the legs. Hence,the body is stable. During normal walking, as the person moves forward with the lifted leg,the other leg must remain firm on the ground to prevent the person from falling (right foot b and left foot e in Figure 4). In a normal individual,powerful contractions of the hip abductors (gluteus medius,gluteus minimus,sartorius,and tensor fasciae latae) hold the suspended body so that it will not fall. However,in a paraplegic these muscles are not strong enough. The trunk will incline from side to side interchangeably to retain the center of gravity within the area of the standing foot (Figure 5). If the hip could be locked in a certain position for a split second,it would increase the stability of one‐foot standing. This can be done relatively easily by hyperextending the trunk (i.e., leaning backward). Two‐legged body stabilization also depends on knee and ankle stability. However,stability from the hip above is already a daunting task for a paraplegic,and thus it seems unlikely that a severely paraplegic individual could stabilize all three joints (hip to ankle). However,stability can be achieved using an ankle/knee (AK) orthosis. With one foot on the ground,the individual can hardly keep the body stable with the center of gravity and within the small area of contact between the foot and ground in order to prevent himself or herself from falling. More often than not,the individual needs to hold a standing frame to ensure stability. Once the lifted leg drops to the ground,the gait cycle of one leg completes and the next cycle begins by lifting the other leg.

The hip is the most important joint with respect to walking. Without hip flexion,the leg cannot move forward and walk. Knee and ankle joint motions are not essential if the leg can be lifted at the hip. During normal walking,a person lifts the foot by bending the thigh at the hip and the leg at the knee (Figure 3b). He or she then swings the leg forward,followed by forward movement of the whole body. This process is assisted by gravity and momentum. A person can walk with a straight leg if the knee and ankle are immobilized. The resulting gait somewhat simulates that of guards during a ceremonial parade (Figure 6).The leg does not need to be lifted to its full range. A little clearance from the ground can suffice to allow a small step forward. Using Grade 3 muscle power according to the British Medical Research Council (MRC),a patient can conduct minimal walking^[6]. This increase in power from Grade 2 to 3 is crucial. It represents the difference between non‐functional and functional,or non‐walkers and walkers. According to the ASIA Standards,such an important improvement or difference is ignored against the convenience of examination in order to avoid inter‐rater discrepancy^[7]. Examination strictly requires the full range for a movement to be qualified for any grade. Thus,this tiny but extremely important difference between nonfunctionality and functionality is lost.

2.3 Dexterity of the hands Walking is not the only important factor for independent living. With the assistance of a wheelchair,a patient and person can move around without much difficulty and thus lead an independent life if his or her arms and hands are sufficiently functional. However,if the level of injury occurs at T1 or above, the patient will encounter difficulties with respect to an independent life. Let us next analyze how the functions of various parts of the upper limb contribute to the minimum required for independent living.

Regarding functions of the upper limbs,none are more important for survival than drinking and eating. Certain steps are required to get drinks and food to the mouth. (1) The person must extend his or her arm to reach the object in front of him or her. This movement involves the shoulder abductors and flexors (Figure 7). Both muscles are innervated by the C5 spinal cord segment. This alone might not be sufficient to reach the object. (2) The individual needs to extend his or her elbow. This motion involves elbow extensors that are innervated by the C7 spinal cord segment (Figure 8). (3) He or she must then graspand hold the object with sufficient power (at least Grade 3 MRC). This is the function of wrist extensors, which are innervated by the C6 spinal cord segment. This function passively increases tension in the finger flexors. These combined functions of the two groups of muscles might provide the individual with sufficient power to hold a light object (Figure 9a). (4) Next,he or she must retract the object to reach his or her mouth. Again,this is a function of the elbow flexors innervated by the C5 spinal cord segment. However, this does not conclude the process,as the object still must reach the mouth and retreat from it after use. For these purposes,forearm rotation is indispensable. Rotation towards the body (pronation) is executed by pronator muscles that are innervated by C5-6 and, to a lesser extent,C8-T1 (Figure 10); rotation away from the body is executed by supinators that are innervated by C7.

From the above‐mentioned description,we observe that if all muscles innervated by spinal cord segments C5-C7 are of Grade 3 MRC,the person can reach drinks and food and thus ensure his or her survival relatively independently. This is the minimum or threshold that should be achieved by cell therapy for repair of the human central nervous system.

3 Practical considerations 3.1 Motor assessment 3.1.1 MRC or ASIA Standards? An improvement of muscle power from Grade 2 to 3 at a certain level of the spinal cord injury makes a difference between life and death. This calls into question the rationale of the ASIA Standards of Motor Examination. This examination requires a full range of movement in a joint in order to qualify a grade of muscle power,thus avoiding ambiguity. This advantage has been offset by the disadvantage of ignoring delicate or even minute changes cross the entire range of joint motion that might make vital contributions to the activities of daily living. Apart from the author’s own observation,a recently reported case of olfactory ensheathing cell transplantation reinforced the view that the traditional British MRC standard underlines a useful increase in muscle power from non‐functional to functional,whereas the ASIA Standards do not^{[6, 7]}. The author wonders if use of the ASIA Standards is responsible for some negative reports concerning olfactory ensheathing cell transplantation^[8]. One might reasonably propose that MRC should be used as a prime standard for measuring the functional outcomes of clinical trials of cell therapy. The ASIA Standards can be used in parallel as a supplement. After accumulating data from a body of clinical trials that have compared these two methods,the resulting conclusion might indicate that only one method is reliable.

3.1.2 A modified walking grading system Regarding walking,the motion must be classified in more detail,rather than a general description of walking. The author would like to propose the following. Walking ability should be based on a test of walking for a distance of 10 meters without falling. This test is not intended to replace the Walking Index for Spinal Cord Injury (WISCI Ⅱ) Descriptors developed by Ditunnos,which are used for rehabilitation^{[9, 10]}. Rather,this newly proposed system is designed specifically and solely for clinical trials of cell therapy. Most recipients of and candidates for cell therapy view standing and walking without human assistance as an essential issue of image. Given this psychological perspective,human assistance is classified as a less satisfactory outcome in this newly proposed system. In addition,the official terminology of orthoses based on the extent of joint immobilization is used instead of the word brace. This system must be tested.

3.2 Level criteria for clinical trials of cell therapy for spinal cord injury The author is aware of only minor improvements in motor functions as described in a limited number of publications from reliable sources and his own observations for more than a decade^{[11, 12, 13, 14]}. For safety reasons,clinical trials of cell transplantation prefer treatment at the thoracic level^{[15, 16]}. However,the ISCoS guidelines also acknowledge that recovery is more likely at the cervical level^[17]. Another concern involves ruling out spontaneous recovery in clinical trials; this is more likely at the cervical level than at the thoracic level. In the latter,the cord is often completely contused in a narrow bony canal,and spontaneous recovery rarely occurs at any stage of the natural course. Thus far,no breakthroughs in major motor improvements at this level have been reported. We do not yet know when such breakthroughs might appear on the horizon. These are definitely not around the corner, and accordingly the journey ahead is long.

From the perspective of independent living,a person injured below the cervical level can receive assistance from a wheelchair,and cell therapy is therefore less urgent. Injury at the cervical level severely compromises independent living. Therefore, repair at this level is a matter of relative urgency. It is absolutely correct that the ISCoS guidelines note that an “improvement of functional abilities,reflected in activities of daily living will be the most meaningful and valued outcome”^[17]. Selection of the cervical cord for a clinical trial is a very different scenario. The cervical cord is enlarged at the most common injury level,C4-6. The cord in this location is very bulky when compared with the thoracic cord,and the incidence of complete severance is low. Hence,recovery is more likely to occur^[18]. Whether recovery is structural or functional is a different issue that requires a very long time to resolve. A recent report described repeated neurological examinations at intervals of at least three months to rule out spontaneous recovery^[12]. If the results of the two examinations are the same, further spontaneous recovery during clinical trial would be considered unlikely. This report falls short of the maximum period of spontaneous recovery of 30 months (more than two years) reported for work conducted by Burns and Ditunno,as well as Waters^{[17, 19, 20]}. Spontaneous recovery may not be a continual process. Interval(s) might occur between episode(s) of recovery, according to the Clinical Database,National Spinal Injuries Centre,Stoke Mandeville Hospital. It might therefore be more reliable to conduct clinical trials after this maximum period to avoid the involvement of spontaneous recovery. Currently,only limited positive results are available after cell therapy,whereas many patients are longing for assistance. If it is ethical to work toward functional improvement,which might benefit a wider population,should the SCI scientific community rethink the strict criteria by which only mid‐thoracic candidates are selected for clinical trials?