**5. Regenerative effects of acupuncture point injection with placental extracts**

Regenerative medicine has the potential to heal or replace tissues and organs damaged by age, disease, or trauma. The current therapy of transplantation of intact organs and tissues to treat organ and tissue failures suffers from limited donor supply and often severe immune complications. These obstacles may potentially be bypassed through the use of regenerative medicine strategies. The field of regenerative medicine encompasses numerous strategies, including use of materials and de novo generated cells, as well as various combinations. Regenerative medicine effectively replaces missing tissues both structurally and functionally, thus contributes to tissue healing. The body's innate healing response may also be leveraged to promote regeneration at the time of regenerative procedure [41].

Placental extracts are obtained by lysing human placental tissues collected from full-term delivery. The extracts do not contain cells but are rich in a wide range of proteins, minerals, amino acids, and steroid hormones. Placenta synthesizes a number of hormones, such as estradiol, progesterone, and chorionic gonadotrophin, which regulate growth and development of the fetus during pregnancy so that placental extracts have the impact on proliferation. Data indicate that placental extracts stimulate proliferation and regenerative processes in various systems. The significant increase in tensile strength and tissue DNA in the animals given human placental extract indicates the extract-induced marked collagen synthesis [42]. Human dermal fibroblasts showed an increased proliferation after treatment of human placental extract [43]. Placental extracts were also shown to enhance the proliferation of cord blood cells in vitro [44]. Animal model studies proved that the placental extract promotes fibrogenesis, neoangiogenesis, and epithelialization [8].

Acupuncture has been used to treat injured tissues and recover the degenerative functions. Experimental results have revealed the positive roles of acupuncture on injury-induced regeneration. Electro-acupuncture was shown to promote the differentiation of endogenous oligodendrocyte precursor cells into oligodendrocytes in the demyelinated spinal cord in rats [45]. In a rat tendon healing model, mechanical stimuli by acupuncture stimulation at the juxtaposition to tenotomized locus appeared to transduce mechanical stimulation to biological changes [46]. It is proposed that the mechanical stimulation by acupuncture leads to increase in small leucine-rich proteoglycan synthesis by fibroblasts close to the injury sites [47]. Clinical application of electroacupuncture increased total cell counts, TGF-β1 and basic fibroblast growth factor (bFGF)-positive cell counts, and the mechanical strength of repaired tendon than the control groups received no treatment [48].

**6.1. Neck and back pain**

the facet joint cavity between C6 and C7.

**Figure 1.** Acupuncture points for treating neck pain.

Neck and back pain most commonly results from injuries to muscles, disks, nerves, ligaments, or facet joints with subsequent inflammation and spasm [54, 55]. Degeneration of disks or joints produces the same symptoms and occurs by aging, previous injury, or excessive mechanical stresses. Herniation of disk tissue produces a profound inflammatory reaction with release of inflammatory chemical mediators especially TNF-α [56]. Subsequent to the release of TNF-α, an increase in the formation of inflammatory mediators such as prostaglandin and nitric oxide as well as phospholipase A2 activation ensues [57]. In sequence, activation of motor nerves that travel from the spinal cord to the muscles results in excessive muscle tension, spasm, and pain. It is accepted that inflammation and the inflammatory response are

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The set of acupuncture points recommended are Ex-HN15, GB21, SI14, and BL10 for neck pain. A sterile 40-mm-long 23 gauge needle is inserted into the acupuncture points at the same time as patients are seated. Ex-HN15 (**Figure 1**), a member of extra channel acupuncture points, is localized on the facet joint between the cervical vertebra 6 (C6) and 7 (C7). From the injury mechanisms during stimulated whiplash, it was revealed that capsular ligament strain reached a maximum at C6-C7 [59]. Through Ex-HN15, 1 mL of placental extract is infused to

Injection to the trigger point–related muscle areas is a good choice for eliminating shortened sarcomeres including contraction knots. Usually, 1 mL of placental extract is injected to the acupuncture points, while needles are inserted to a depth of 25 mm, which is deep enough

responsible for neck and back pain both with and without herniated disk [58].

API with placental extract has two advantages; acupuncture stimulation *per se* and pharmacological effect of placental extract. As a needle of acupuncture arrives at the site of injured or degenerative locus with placental extract, a regenerative event begins. It is asserted that a combined therapy of acupuncture and placental extract stimulates regeneration more vigorously in injured or degenerative tissues than the separate application does.
