Objective: The aim of this study was to investigate if adipose-derived stromal vascular fraction (SVF) treatment has any protective effect on ovarian function in rats with cyclophosphamide (CP) induced ovarian damage. Design: This was an experimental animal study. Participants/Materials, Setting, Methods: 25 mature cycling Wistar-Albino rats were randomized into four groups (n = 5 per group). Rats in groups 1 and 2 received single dose of intraperitoneal (i.p.) 1 mL/kg sodium chloride 0.9% (NaCl). Groups 3 and 4 received single dose of 75 mg/kg i.p. CP. On seventh day, SVF was prepared from adipose tissues of 5 additional rats and groups 1 and 3 received 0.9% NaCl i.p. injections while groups 2 and 4 received 0.2 mL i.p. injections of SVF. On day 21 all rats were euthanized, and serum anti-mullerian hormone (AMH) levels, primordial, primary, secondary, antral, and atretic follicle counts, AMH positive staining follicle counts along with AMH staining intensity of the follicles were evaluated. Results: Among two CP induced ovarian damaged groups, SVF treated group showed significantly higher secondary and antral follicle and lower atretic follicle counts, significantly higher mean serum AMH levels, AMH positive antral follicle count and higher intensity of AMH positive follicle scores for primary, secondary, and antral follicles when compared to untreated group. Moreover, group 1 showed no significant difference for all parameters except antral follicle count and AMH positive staining intensity scores for antral follicles when compared to group 4. Limitations: This study was conducted on experimental rat model. Conclusion: Our study demonstrated a significant protective effect of SVF against CP-induced ovarian damage which reveals the apparent need for further investigation of its precise mechanisms of action as it may provide a new treatment approach for women with premature ovarian failure.

1.
Fritz
R
,
Jindal
S
.
Reproductive aging and elective fertility preservation
.
J Ovarian Res
.
2018
;
11
(
1
):
66
.
2.
Kovanci
E
,
Schutt
AK
.
Premature ovarian failure: clinical presentation and treatment
.
Obstet Gynecol Clin North Am
.
2015
;
42
(
1
):
153
61
.
3.
Shelling
AN
.
Premature ovarian failure
.
Reproduction
.
2010
;
140
(
5
):
633
41
.
4.
Özcan
P
,
Fıçıcıoğlu
C
,
Yıldırım
ÖK
,
Özkan
F
,
Akkaya
H
,
Aslan
İ
.
Protective effect of resveratrol against oxidative damage to ovarian reserve in female Sprague-Dawley rats
.
Reprod Biomed Online
.
2015
;
31
(
3
):
404
10
.
5.
Özcan
P
,
Fıçıcıoğlu
C
,
Kizilkale
O
,
Yesiladali
M
,
Tok
OE
,
Ozkan
F
, et al
.
Can Coenzyme Q10 supplementation protect the ovarian reserve against oxidative damage
.
J Assist Reprod Genet
.
2016
;
33
(
9
):
1223
30
.
6.
Yurttancikmaz
ET
,
Ozcan
P
,
Tanoglu
FB
,
Tok
OE
,
Timur
HT
,
Cetin
C
.
Protective effect of glutathione administration on ovarian function in female rats with cyclophosphamide-induced ovarian damage
.
Gynecol Obstet Invest
.
2024
;
89
(
2
):
120
30
.
7.
Meldrum
DR
.
Aging gonads, glands, and gametes: immutable or partially reversible changes
.
Fertil Steril
.
2013
;
99
:
1
4
.
8.
Petryk
N
,
Petryk
M
.
Ovarian rejuvenation through platelet-rich autologous plasma (PRP)-a chance to have a baby without donor eggs, improving the life quality of women suffering from early menopause without synthetic hormonal treatment
.
Reprod Sci
.
2020
;
27
(
11
):
1975
82
.
9.
Gupta
S
,
Lodha
P
,
Karthick
MS
,
Tandulwadkar
SR
.
Role of autologous bone marrow-derived stem cell therapy for follicular recruitment in premature ovarian insufficiency: review of literature and a case report of world’s first baby with ovarian autologous stem cell therapy in a perimenopausal woman of age 45 year
.
J Hum Reprod Sci
.
2018
;
11
(
2
):
125
30
.
10.
Caplan
AI
.
Mesenchymal stem cells
.
J Orthop Res
.
1991
;
9
(
5
):
641
50
.
11.
Zuk
PA
,
Zhu
M
,
Ashjian
P
,
De Ugarte
DA
,
Huang
JI
,
Mizuno
H
, et al
.
Human adipose tissue is a source of multipotent stem cells
.
Mol Biol Cell
.
2002
;
13
(
12
):
4279
95
.
12.
Abdi
R
,
Fiorina
P
,
Adra
CN
,
Atkinson
M
,
Sayegh
MH
.
Immunomodulation by mesenchymal stem cells: a potential therapeutic strategy for type 1 diabetes
.
Diabetes
.
2008
;
57
(
7
):
1759
67
.
13.
Prockop
DJ
,
Kota
DJ
,
Bazhanov
N
,
Reger
RL
.
Evolving paradigms for repair of tissues by adult stem/progenitor cells (MSCs)
.
J Cell Mol Med
.
2010
;
14
:
2190
9
.
14.
Mitrano
TI
,
Grob
MS
,
Carrion
F
,
Nova-Lamperti
E
,
Luz
PA
,
Fierro
FS
, et al
.
Culture and characterization of mesenchymal stem cells from human gingival tissue
.
J Periodontol
.
2010
;
81
(
6
):
917
25
.
15.
Wei
X
,
Yang
X
,
Han
Z
,
Qu
F
,
Shao
L
,
Shi
Y
.
Mesenchymal stem cells: a new trend for cell therapy
.
Acta Pharmacol Sin
.
2013
;
34
(
6
):
747
54
.
16.
Bourin
P
,
Bunnell
BA
,
Casteilla
L
,
Dominici
M
,
Katz
AJ
,
March
KL
, et al
.
Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT)
.
Cytotherapy
.
2013
;
15
(
6
):
641
8
.
17.
Ozcan
P
,
Takmaz
T
,
Tok
OE
,
Islek
S
,
Yigit
EN
,
Ficicioglu
C
.
The protective effect of platelet-rich plasma administrated on ovarian function in female rats with Cy-induced ovarian damage
.
J Assist Reprod Genet
.
2020
;
37
(
4
):
865
73
.
18.
Kurzyk
A
,
Dębski
T
,
Święszkowski
W
,
Pojda
Z
.
Comparison of adipose stem cells sources from various locations of rat body for their application for seeding on polymer scaffolds
.
J Biomater Sci Polym Ed
.
2019
;
30
(
5
):
376
97
.
19.
Tilly
JL
.
Ovarian follicle counts: not as simple as 1, 2, 3
.
Reprod Biol Endocrinol
.
2003
;
1
:
11
.
20.
Zhang
T
,
Yan
D
,
Yang
Y
,
Ma
A
,
Li
L
,
Wang
Z
, et al
.
The comparison of animal models for premature ovarian failure established by several different source of inducers
.
Regul Toxicol Pharmacol
.
2016
;
81
:
223
32
.
21.
Leng
L
,
Tan
Y
,
Gong
F
,
Hu
L
,
Ouyang
Q
,
Zhao
Y
, et al
.
Differentiation of primordial germ cells from induced pluripotent stem cells of primary ovarian insufficiency
.
Hum Reprod
.
2015
;
30
(
3
):
737
48
.
22.
Hao
X
,
Anastácio
A
,
Liu
K
,
Rodriguez-Wallberg
KA
.
Ovarian follicle depletion induced by chemotherapy and the investigational stages of potential fertility-protective treatments-A review
.
Int J Mol Sci
.
2019
;
20
(
19
):
4720
.
23.
Roness
H
,
Kashi
O
,
Meirow
D
.
Prevention of chemotherapy-induced ovarian damage
.
Fertil Steril
.
2016
;
105
(
1
):
20
9
.
24.
Kalich-Philosoph
L
,
Roness
H
,
Carmely
A
,
Fishel-Bartal
M
,
Ligumsky
H
,
Paglin
S
, et al
.
Cyclophosphamide triggers follicle activation and “burnout”; AS101 prevents follicle loss and preserves fertility
.
Sci Transl Med
.
2013
;
5
(
185
):
185ra62
.
25.
Bedoschi
G
,
Navarro
PA
,
Oktay
K
.
Chemotherapy-induced damage to ovary: mechanisms and clinical impact
.
Future Oncol
.
2016
;
12
(
20
):
2333
44
.
26.
Yoshimura
K
,
Shigeura
T
,
Matsumoto
D
,
Sato
T
,
Takaki
Y
,
Aiba-Kojima
E
, et al
.
Characterization of freshly isolated and cultured cells derived from the fatty and fluid portions of liposuction aspirates
.
J Cell Physiol
.
2006
;
208
(
1
):
64
76
.
27.
Dykstra
JA
,
Facile
T
,
Patrick
RJ
,
Francis
KR
,
Milanovich
S
,
Weimer
JM
, et al
.
Concise review: fat and furious: harnessing the full potential of adipose-derived stromal vascular fraction
.
Stem Cells Transl Med
.
2017
;
6
(
4
):
1096
108
.
28.
Rehman
J
,
Traktuev
D
,
Li
J
,
Merfeld-Clauss
S
,
Temm-Grove
CJ
,
Bovenkerk
JE
, et al
.
Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells
.
Circulation
.
2004
;
109
(
10
):
1292
8
.
29.
Traktuev
DO
,
Prater
DN
,
Merfeld-Clauss
S
,
Sanjeevaiah
AR
,
Saadatzadeh
MR
,
Murphy
M
, et al
.
Robust functional vascular network formation in vivo by cooperation of adipose progenitor and endothelial cells
.
Circ Res
.
2009
;
104
(
12
):
1410
20
.
30.
Traktuev
DO
,
Merfeld-Clauss
S
,
Li
J
,
Kolonin
M
,
Arap
W
,
Pasqualini
R
, et al
.
A population of multipotent CD34-positive adipose stromal cells share pericyte and mesenchymal surface markers, reside in a periendothelial location, and stabilize endothelial networks
.
Circ Res
.
2008
;
102
(
1
):
77
85
.
31.
Koh
YJ
,
Koh
BI
,
Kim
H
,
Joo
HJ
,
Jin
HK
,
Jeon
J
, et al
.
Stromal vascular fraction from adipose tissue forms profound vascular network through the dynamic reassembly of blood endothelial cells
.
Arterioscler Thromb Vasc Biol
.
2011
;
31
(
5
):
1141
50
.
32.
Zeyda
M
,
Farmer
D
,
Todoric
J
,
Aszmann
O
,
Speiser
M
,
Györi
G
, et al
.
Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production
.
Int J Obes
.
2007
;
31
(
9
):
1420
8
.
33.
Mills
CD
.
M1 and M2 macrophages: oracles of health and disease
.
Crit Rev Immunol
.
2012
;
32
(
6
):
463
88
.
34.
Sakaguchi
S
,
Yamaguchi
T
,
Nomura
T
,
Ono
M
.
Regulatory T cells and immune tolerance
.
Cell
.
2008
;
133
(
5
):
775
87
.
35.
Cipolletta
D
,
Kolodin
D
,
Benoist
C
,
Mathis
D
.
Tissular T(regs): a unique population of adipose-tissue-resident Foxp3+CD4+ T cells that impacts organismal metabolism
.
Semin Immunol
.
2011
;
23
(
6
):
431
7
.
36.
Salvatore
G
,
De Felici
M
,
Dolci
S
,
Tudisco
C
,
Cicconi
R
,
Campagnolo
L
, et al
.
Human adipose-derived stromal cells transplantation prolongs reproductive lifespan on mouse models of mild and severe premature ovarian insufficiency
.
Stem Cell Res Ther
.
2021
;
12
(
1
):
537
.
37.
Shah
FS
,
Wu
X
,
Dietrich
M
,
Rood
J
,
Gimble
JM
.
A non-enzymatic method for isolating human adipose tissue-derived stromal stem cells
.
Cytotherapy
.
2013
;
15
(
8
):
979
85
.
38.
Raposio
E
,
Caruana
G
,
Bonomini
S
,
Libondi
G
.
A novel and effective strategy for the isolation of adipose-derived stem cells: minimally manipulated adipose-derived stem cells for more rapid and safe stem cell therapy
.
Plast Reconstr Surg
.
2014
;
133
(
6
):
1406
9
.
39.
Aronowitz
JA
,
Lockhart
RA
,
Hakakian
CS
.
Mechanical versus enzymatic isolation of stromal vascular fraction cells from adipose tissue
.
Springerplus
.
2015
;
4
:
713
.
40.
Freese
KE
,
Kokai
L
,
Edwards
RP
,
Philips
BJ
,
Sheikh
MA
,
Kelley
J
, et al
.
Adipose-derived stems cells and their role in human cancer development, growth, progression, and metastasis: a systematic review
.
Cancer Res
.
2015
;
75
(
7
):
1161
8
.
41.
Yoon
SY
.
Mesenchymal stem cells for restoration of ovarian function
.
Clin Exp Reprod Med
.
2019
;
46
:
1
7
.
42.
Faustini
M
,
Bucco
M
,
Chlapanidas
T
,
Lucconi
G
,
Marazzi
M
,
Tosca
MC
, et al
.
Nonexpanded mesenchymal stem cells for regenerative medicine: yield in stromal vascular fraction from adipose tissues
.
Tissue Eng C Methods
.
2010
;
16
(
6
):
1515
21
.
43.
Lee
SY
,
Shin
JE
,
Kwon
H
,
Choi
DH
,
Kim
JH
.
Effect of autologous adipose-derived stromal vascular fraction transplantation on endometrial regeneration in patients of Asherman’s syndrome: a pilot study
.
Reprod Sci
.
2020
;
27
(
2
):
561
8
.
You do not currently have access to this content.