Page 20 - Human Umbilical Cord Mesenchymal Stem Cells

HARVESTABLE MESENCHYMAL STEM CELLS 1839

adipose tissue, and unprocessed lipoaspirate and simple standard density for bone marrow used for conversions
adipose tissue were evaluated as equivalent substances. was determined to be 1.058 g/mL. 23 Values from
Levels for adipose-derived MSCs ranged from 4,737.5 studies that did not include volume or mass data for
MSCs/mL of lipoaspirate 13 to 1,550,000 MSCs/mL of bone marrow harvest could not be reported in millili-
lipoaspirate 14 (Table 1, Fig 1). ters and, consequently, were reported with MSCs as a
percentage of total nucleated cells. Similar concerns
Bone Marrow arose in the reporting of umbilical cord tissue. Values
Bone marrow tissue harvest was primarily conducted from studies that did not include mass or volume data
through repeated aspirations through large-bore nee- were instead recorded by length of cord and could not
dles, ranging from 15- to 18-gauge sizes. 15 Levels for be converted.
bone marrowederived MSCs ranged from 1 to 30
MSCs/mL 15 to 317,400 cells/mL 16 (Table 1, Fig 1). Autograft Tissue and Minimal Manipulation
Comparisons of yields between placental and autograft
Umbilical Cord and Placental Tissue
tissue invite clarification of the practical difference be-
Placental tissuee and umbilical cordederived MSCs
tween autograph and allograph transplantation, as well
proved unique in their diverse harvest and tissue-specific
as minimally manipulated tissues. Allograft tissue rarely
harvest sites. Tissue cell levels for Wharton’s jelly (um-
presents with immune complications after trans-
bilical cord connective tissue) ranged from 10,000 MSCs/ plantation. The lack of the human leukocyte antigeneA
mL of umbilical cord 17 to 4,700,000 MSCs/cm of umbil- surface antigen confers an immune-privileged nature to
18
ical cord. Chorionic tissue cell levels were reported to be placental tissue, allowing for comparable use of the 2
45,000 MSCs/g of wet tissue (Fig 1). 19 24
tissues without immune-modifying therapy. Conse-
quently, for the purposes of clinical use and this review,
Peripheral Tissue
allograft placental tissue is comparable with autograft
Peripheral blood, which was collected through pe-
cells.
ripheral blood draw and centrifugation, was reported to According to US Food and Drug Administration (FDA)
have MSC levels of 1 to 40 cells/mL. 20 Muscle tissue
regulations, only cellular products classified as “361 tis-
was harvested from the semitendinosus tendon, which sue” may be exempt from premarket review and regu-
was collected with a tendon stripper. 21 Similarly, peri-
lation. Classification as 361 tissue requires cells to be
osteum tissue was collected from the tibial insertion of “minimally manipulated,” a criterion that excludes
the same harvested semitendinosus tendon. 21 Synovial
many common techniques used to harvest, isolate, and
tissue was harvested during arthroscopic surgery from
purify MSCs today. It should be noted that adipose tissue
the medial joint capsule of the knee using a pituitary currently harvested for MSCs requires multistep pro-
rongeur. 21
cessing, including enzymatic digestion, purification, and
expansion in culture, which is considered more than
Discussion “minimal manipulation,” thereby excluding them from
25
The advancement of stem cell transplant techniques 361 cellular tissue classification by the FDA. However,
over recent years has made the practical acquisition of recent procedural and technologic advances have
these cells increasingly worthwhile for the purpose of demonstrated efficient, non-enzymatic purification of
reconstructive surgery. Autologous sources represent human MSCs from lipoaspirate. 26 Further, recent
the most current, cost-efficient, and least controversial studies have shown mechanically purified adipose-
option to acquire and transplant MSCs in the clinical derived MSCs demonstrate greater pluripotent response
setting. Physicians and researchers exploring this compared to enzymatically isolated adipose stem cells. 27
emerging field will require resources concisely Given recent FDA approval for marketing of this system
explaining the most efficient sites for MSC harvest, as and subsequent “361 cellular tissue” classification, the
well as the levels of cells available in different tissues. field of adipose-derived stem cells and their clinical
Determining the best and most consistent tissue source application may greatly expand in the coming years. In
of human MSCs, as well as the cell levels typically addition, a 2013 update by the FDA Tissue Reference
harvested from related sites, offers a valuable resource Group clarified that bone marrow MSCs, when
for future clinical studies. expanded in culture, did not fall under the classification
Given the diverse array of units used to report cell of 361 cells. 28 Consequently, the advancement of the
harvest levels among selected studies, values were field and therapeutic application of MSCs will likely rely
converted to a standard measurement to allow direct on the ability to harvest cells in quantities suitable for
comparison between studies and tissues. For adipose implantation without digestion and expansion. A
values, a common value for the density of adipose detailed understanding of the anatomic sites and tissue
tissue was selected from previous studies as 0.9475 types yielding the highest levels and concentrations of
g/mL 22 to convert values from grams to milliliters. The cells by volume will prove crucial to these initial steps.