The Long Path of Human Placenta, and Its Derivatives, in Regenerative Medicine

Abstract

In the 1800s, a baby born with a caul, a remnant of the amniotic sack or fetal membranes, was thought to be lucky, special, or protected. Over time, fetal membranes lost their legendary power and were soon considered nothing more than biological waste after birth. However, placenta tissues have reclaimed their potential and since the early 1900s an increasing body of evidence has shown that these tissues have clinical benefits in a wide range of wound repair and surgical applications. Nowadays, there is a concerted effort to understand the mechanisms underlying the beneficial effects of placental tissues, and, more recently, cells derived thereof. This review will summarize the historical and current clinical applications of human placental tissues, and cells isolated from these tissues, and discuss some mechanisms thought to be responsible for the therapeutic effects observed after tissue and/or cell transplantation.

Keywords: amniotic and chorionic membranes; clinical trials; human term placenta; immunomodulation; paracrine effect; regenerative medicine; stem cells; umbilical cord.

Figure 1

Historical uses of human term placental tissues and cells derived thereof. ¹Chinese medical text published in 1593 by Li Shi-Zhen; ²Davis (1910) and Stern (1913) and Sabella (1913); ³Brindeau (1934) and Burger (1937); ⁴De Rotth (1940), Sorsby and Symons (1946); Sorsby et al. (1947); ⁵Dino et al. (1965); ⁶Trelford-Sauder et al. (1977); Trelford-Sauder et al. (1978), Silverton et al. (1979); Dhall (1984), Nisolle and Donnez (1992), Georgy and Aziz (1996), Gharib et al. (1996); ⁷Trelford-Sauder et al. (1978); Muralidharan et al. (1991), Young et al. (1991); Arora et al. (1994), Rennekampff et al. (1994); ⁸Troensagaard-Hansen (1950); Bennett et al. (1980), Subrahmanyam (1995); ⁹Gruss and Jirsch (1978) and Bose (1979); ¹⁰Lee and Tseng (1997); Tseng et al. (1997), ^{11, 12} reviewed in Fetterolf and Snyder (2012).

Figure 2

Registered clinical trials using placenta-derived cells or amniotic membrane. The search was performed in June 2015 on the U.S. National Institutes of Health clinical trials website using: placental-derived cells OR amniotic membrane, which resulted in 240 clinical trials. After excluding those with unknown status (which resulted in 196) and irrelevant ones, the search resulted in 95 clinical trials. For each disease application specified in small boxes, n = 1 unless otherwise specified. PAD, peripheral arterial disease; EB, epidermolysis bullosa; IPF, idiopathic pulmonary fibrosis; RA, rheumatoid arthritis; GvHD, graft versus host disease *Includes two published clinical trials not registered on NIH website (diabetes and multiple sclerosis).