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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 16  |  Issue : 4  |  Page : 360-370

The role of human umbilical cord blood stem cells in modifying the effect of experimentally induced myocardial infarction in male albino rats


1 Department of Physiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
2 Department of Biochemistry, Faculty of Medicine, Zagazig University, Zagazig, Egypt
3 Department of Cardiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Date of Submission29-Jul-2018
Date of Acceptance27-Jan-2019
Date of Web Publication23-Apr-2019

Correspondence Address:
Randa S Gomaa
Department of Medical Physiology, Faculty of Medicine, Zagazig University, Zagazig, 44519
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AZMJ.AZMJ_73_18

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  Abstract 


Background Ischemic heart diseases are considered as the first cause of death around the world. Mesenchymal stem cells are considered to be a novel therapy that can achieve real success in myocardial infarction (MI).
Objective Evaluating the homing capability of human umbilical cord blood stem cells (HUCBSCs) in the injured myocardium and its role in the development of MI in adult male rats.
Materials and methods Fifty adult male albino rats were divided into five groups (n=10): control, MI, MI pretreated with HUCBSCs, MI posttreated with HUCBSCs within 24 h, and MI posttreated with HUCBSCs within 1 week. Serum cardiac troponin I and creatine kinase-myoglobin binding levels were evaluated to assess MI induction. Gene expression of human β actin gene was assessed to evaluate HUCBSCs homing and rat caspase-3 gene was assessed to evaluate apoptosis. Myocardial histopathological examination was done to assess fibrosis. Echocardiographic left ventricular dimensions and function and mean arterial blood pressure were assessed.
Results β actin gene expression was higher in all HUCBSCs injected groups compared with normal and MI groups. Administration of HUCBSCs decreased caspase-3 gene expression and fibrosis and improved cardiac function and mean arterial blood pressure in all HUCBSCs injected groups compared with the MI group and these effects were more in pretreated group than both posttreated groups. Expression of rat caspase-3 gene, histopathological assessment, and echocardiography results showed more improvement in posttreated within 24 h group than posttreated within 1-week group.
Conclusion HUCBSCs have high homing capability in injured myocardium and they could be used as a preventive therapy in case of ischemia to protect the heart from implications of MI. Moreover, it could be an effective therapy especially if administered within 24 h after MI. Further studies are recommended to highlight the preventive role of HUCBSCs and its clinical application especially in cases of unstable angina.

Keywords: animal model, mesenchymal stem cells, myocardial infarction


How to cite this article:
Tawfeeq MS, Ibrahim SM, Abd Allah SH, Gomaa RS, Salama AE, WahidEldin RM. The role of human umbilical cord blood stem cells in modifying the effect of experimentally induced myocardial infarction in male albino rats. Al-Azhar Assiut Med J 2018;16:360-70

How to cite this URL:
Tawfeeq MS, Ibrahim SM, Abd Allah SH, Gomaa RS, Salama AE, WahidEldin RM. The role of human umbilical cord blood stem cells in modifying the effect of experimentally induced myocardial infarction in male albino rats. Al-Azhar Assiut Med J [serial online] 2018 [cited 2019 Aug 23];16:360-70. Available from: http://www.azmj.eg.net/text.asp?2018/16/4/360/256763




  Introduction Top


Myocardial infarction (MI) is defined as a clinical event caused by coronary artery occlusion that leads to myocardial ischemia with evidence of myocardial injury or necrosis [1]. Cardiomyocytes that die are replaced by scar tissue and many studies reported that mammalian myocardium has an intrinsic capacity to regenerate by endogenous stem cells. However, the magnitude and capacity of this response seems to be minimal and has to be realized [2]. The difficulty in regenerating damaged myocardium has motivated researchers to find out a novel stem-cell- based therapy and explore the application of different types of stem cells for cardiac repair [3].

Mesenchymal stem cells (MSCs) including bone marrow MSCs, adipose tissue-derived MSCs, and human umbilical cord blood stem cells (HUCBSCs) are classified as adult-derived stem cells that give rise to different tissues such as the muscle, bone, tendons, and adipose tissue [3]. MSCs isolated from the umbilical cord blood are obtained easily, do not induce immunological reaction, and have good plasticity and proliferative capacity [4].

There are clinical studies that investigate the potential of stem-cell-based therapy in the treatment of MI. These clinical studies have demonstrated a good safety profile and improved cardiac function in patients with MI [5],[6]. Other studies reported that clinical application of MSC-based therapy is restricted and not highly effective and this restriction is attributed to the poor viability of the transplanted cells in the myocardium [7]. In addition, Gyongyosi et al. [8] meta-analysis results showed no efficacy regarding stem-cell therapy in MI.

On the basis of these data, investigating the homing capability of HUCBSCs in the injured myocardium and evaluating its role in the development of MI in adult male rats is the objective of the current study.


  Materials and methods Top


Animals

Fifty adult male albino rats of 12–14 weeks old weighing 180–220 g were provided from the Animal House Faculty of Veterinary Medicine, Zagazig University. They were kept in steel wire cages in the animal house in the Faculty of Medicine, Zagazig University under hygienic conditions. Animals had free access to water, fed on commercial rat standard chow, kept at room temperature, and were maintained on a 12 h light/dark cycle. The rats were accommodated to animal house conditions for 1 : 2 weeks before the experiment [9]. The experimental protocols were approved by the Physiology Department and by the Institutional Review Board (IRB) Committee, Faculty of Medicine, Zagazig University, Egypt.

The animals were divided into five equal groups:

Group I (control): rats received distilled water (1 ml) subcutaneously once daily for 2 consecutive days (24 h apart).

Group II (MI): rats received adrenaline (Sigma-Aldrich, Saint Louis, USA) 2 mg/kg subcutaneously once daily for 2 consecutive days (24 h apart) for induction of MI [10]. Rats received, 1 ml of PBS intravenous injection once in the tail veins 24 h from MI induction.

Group III (MI pretreated with HUCBSCs): as group II but rats received 2×106 cells/dose HUCBSCs intravenous injection once in the tail veins [11] before the second dose of adrenaline and after ECG confirmation of ischemia (inverted T wave) ([Figure 1]).
Figure 1 ECG tracing in group III showing ischemia (inverted T wave).

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Group IV (MI posttreated with HUCBSCs within 24 h): as group II but the rats received 2×106 cells/dose HUCBSCs intravenous injection once at the end of the first 24 h from MI induction.

Group V (MI posttreated with HUCBSCs within 1 week): as group II but the rats received 2×106 cells/dose HUCBSCs intravenous injection once at the end of the first week from MI induction.

For all groups the following was done:

Blood samples were collected by ocular vein puncture within 24 h from MI induction. The clean sera were analyzed for cardiac troponin I (cTn-I) and creatine kinase-myoglobin binding (CK-MB).

After 8 weeks from induction of MI, the mean arterial blood pressure (MABP) measurement and echocardiography assessment were done and then the animals were killed by decapitation under anesthesia (chloral hydrate) inhalation; the hearts were dissected. Histopathological examination of the myocardial tissue, gene expression of human β actin gene expression, and rat caspase-3 gene were assessed in the cardiac tissues of all groups by PCR.

Human umbilical cord blood stem cells preparation

HUCB was obtained after full-term normal vaginal deliveries with informed patient consent and full ethical approval at Gynecology and Obstetrics Department, Faculty of Medicine, Zagazig University using the method of Tang et al. [12]. Cord blood samples were diluted in Dulbecco’s Modified Eagle’s Medium (Sigma Aldrich) and centrifuged. The interphase, mononuclear cells were collected and washed with PBS and then suspended in ammonium chloride buffer for lysis of RBCs. Cell viability was assessed by the trypan blue dye. Cells were plated in Dulbecco’s Modified Eagle’s Medium with 30% fetal calf serum (Sigma Aldrich), dexamethasone (10−7 M; Sigma Aldrich), penicillin (100 U/ml; Lonza Bioproducts, Walkersville, Maryland, USA), streptomycin (0.1 mg/ml; Lonza Bioproducts), and ultraglutamine (2 mmol; Lonza Bioproducts). Cells were incubated at 37°C in 5% CO2 in a humidified atmosphere. When cells reached 80% confluency, they were detached with 0.25% trypsin.

Characterization of HUCBSCs was conducted by determination of surface markers and evaluating the positive expression of CD105 surface marker and the negative expression of CD34 surface marker in HUCBSCs by flow cytometer analysis [13]. This procedure was conducted in collaboration with the Clinical Pathology Department, Faculty of Medicine, Zagazig University. The mononuclear cells were collected by centrifugation for 5 min, washed once with PBS, and resuspended in 1 ml PBS. Three samples were prepared. The first was stained by polyclonal human anti-CD34 (Sigma Aldrich), the second was stained by polyclonal human anti-CD105 antibodies, and the third was prepared by PBS as a negative control. After 20 min of incubation, the stained cells were analyzed using a FACSCalibur Flow Cytometer and Cell Quest software (BD, Biosciences, San Jose, USA).

HUCBSCs injections were prepared from colonies of the second generation of HUCBSCs that were washed twice with PBS and then trypsinized with 0.25% trypsin in 1 ml EDTA for 5 min at 37°C. After centrifugation for 20 min, the cells were counted under a microscope by a hemocytometer and the calculated doses were injected immediately into the tail vein of each animal.

Sampling of blood and serum analysis

Blood samples were collected by ocular vein puncture within 24 h from MI and allowed to clot for 2 h at room temperature before centrifugation. Sera were stored at −20°C until analysis. Repeated freezing and thawing were avoided.

Estimation of serum CK-MB level was done by using rat ELISA kits (Pointe Scientific Inc., Detroit, Michigan, USA) as described by Christenson et al. [14]. The serum cTn-I level was done by using rat ELISA Kits (Sun Red, Shanghai, China) as described by Desai et al. [15].

Cardiac function assessments

Echocardiographic study

Echocardiographic study was performed 8 weeks after MI. The echocardiographic procedure was performed as described by Azar et al. [16]. A commercially available echocardiographic system with a 12-MHz probe (Philips Ultrasound, Harrisburg, Pennsylvania, USA) was used to obtain the measurements. Images were obtained from the left parasternal short-axis views of the left ventricle (LV) at the level of papillary muscles to define internal diameters during systole and diastole. Left ventricular end-diastolic dimension (LVEDd) and end-systolic dimension (LVESd) were measured for at least three consecutive cardiac cycles. Left ventricular fractional shortening (LVFS) was calculated as [(LVEDd−LVESd)/LVEDd]×100% and left ventricular ejection fraction (LVEF) were determined as [(LVEDd3−LVESd3)/LVEDd3]×100%.

Measurement of mean arterial blood pressure

Mean arterial blood pressure measurement was done by the tail-cuff device (NARCO; Biosystem Inc., Lewisville, Texas, USA) after the animals have been warmed for 30 min in a metabolic chamber maintained at approximately 30°C. The mean values of MABP obtained from three consecutive measurements were recorded as the pressure value for each rat.

Histopathological examination

It was done with collaboration of the Pathology Department, Faculty of Medicine, Zagazig University. All rats were killed after endpoint cardiac function assessment being recorded and then the hearts were removed and fixed in 10% formalin. The hearts were cut into 5 µm paraffin sections at the mid-LV level. Masson’s trichrome stain to quantify the extent of fibrosis was performed and the percentage of the fibrotic area was calculated as (fibrotic length/LV circumference)×100% [17]. Hematoxylin-eosin (H&E) stain to evaluate the pathological changes was performed [18]. At least three sections from each heart were stained.

Reverse transcription polymerase chain reaction

Total mRNA was extracted from the frozen heart by using RNA Extraction Kit, (Sigma Aldrich) according to the manufacturer’s instruction; complementary DNA was produced from the total RNA using the complementary DNA synthesis kit (Sigma Aldrich). Primers were as follows.

Human β actin gene [19]:

Forward 5′-GTTGCTATCCAGGCT GTG- 3′

Reverse 5′-TGATCTTGATCTTCATTGTG-3′

Rat caspase-3 gene [20]:

Forward

5′-ATGGACAACAACGAAACCTC-3′

Reverse

5′-TTAGTGATAAAAGTACAGTTCTT-3′

The PCR reactions included reverse transcription at 50°C for 30 min, initial denaturation at 94°C for 2 min, followed by 35 cycles with 94°C for 50 s, 58°C for 50 s, and 65°C for 1 min. The reactions were terminated by 65°C for 10 min as a final extension. PCR products were separated by electrophoresis in 1% agarose gel. The semiquantitative analysis was made depending on the optical density of each band [21].

Statistical analysis

The results were presented as mean±SD. Statistical analysis was performed using the Statistical Package for the Social Sciences, version 19.0 (SPSS Inc., Chicago, Illinois, USA). Repeated measures of analysis of variance was applied followed by least significance differences for multiple comparisons. Levels of significance (P) were considered to be statistically significant when the P value is less than 0.05 [22].


  Results Top


Expression of surface markers of mesenchymal stem cells by flow cytometry

About 50% isolated cells showed only CD105-positive expression, while all cells showed a negative expression of CD34 surface markers ([Figure 2]).
Figure 2 Flow-cytometric analysis of cell surface markers in HUCBSCs. HUCBSCs, human umbilical cord blood stem cells.

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Tracing of cardiac homing of injected human umbilical cord blood stem cells

Mean±SD of human β actin gene expression density was 4500±1394, 4750±1296, 25 300±5538, 29 100±4794, and (26 100±5279) in groups I, II, III, IV, and V, respectively. There was a significant increase in human β actin gene expression when all HUCBSCs treated groups were compared with control and MI groups (P<0.001) ([Figure 3]).
Figure 3 RT-PCR analysis of human β actin gene expression in all studied groups. n=10 in each group. Data are represented as mean±SD. Significance (P<0.05). *Significant when compared with the control group; #significant when compared with group II. RT, reverse transcription.

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Effect of human umbilical cord blood stem cells on cardiac enzymes

Mean±SD of serum cTn-I levels were 0.01±0.005, 0.15±0.03, 0.079±0.02, 0.16±0.04, and 0.19±0.05 ng/ml in groups I, II, III, IV, and V, respectively ([Figure 4]a).
Figure 4 Comparison of cardiac enzymes level (a) cTn-I and (b) CK-MB in all studied groups. n=10 in each group. Data are represented as mean±SD. cTn-I, cardiac troponin I; CK-MB, creatine kinase-myoglobin binding. Significance (P<0.05). *Significant when compared with the control group; #significant when compared with group II; $significant when compared with group III.

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Mean±SD of CK-MB levels were 4.6±1.8, 40.4±7.5, 21.9±6.3, 39.8±6.3, and 38.5±6.1 ng/ml in groups I, II, III, IV, and V, respectively ([Figure 4]b).

There was a significant increase in both enzymes when all groups were compared with the control group (P<0.001). There was a significant decrease in both enzymes when HUCBSCs pretreated group (P<0.01) with insignificant change and when both HUCBSCs posttreated groups were compared with the MI group (P>0.05). However, there was a significant increase in both enzymes when both HUCBSCs posttreated groups were compared with HUCBSCs pretreated group (P<0.001).

Effect of human umbilical cord blood stem cells on apoptosis in the myocardium

Mean±SD of rat caspase-3 gene expression density was 4050±1091, 29 100±4794, 11 500±3778, 19 800±3047, and 23 000±2828 in groups I, II, III, IV, and V, respectively.

There was a significant increase in caspase-3 gene expression in all groups when compared with the control group (P<0.001). Moreover, there was a significant decrease in caspase-3 gene expression in all HUCBSCs treated groups when compared with the MI group (P<0.001). In addition, there was a significant increase of caspase-3 gene expression in both HUCBSCs posttreated groups when compared with HUCBSCs pretreated group (P<0.001) and a significant increase in its expression when HUCBSCs posttreated within 1-week group was compared with HUCBSCs posttreated within 24 h group (P<0.05) ([Figure 5]).
Figure 5 RT-PCR analysis of rat caspase-3 gene expression in all studied groups. n=10 in each group. Data are represented as mean±SD. Significance (P<0.05). *Significant when compared with the control group; #significant when compared with group II; $significant when compared with group III; @significant when compared with group IV. RT, reverse transcription.

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Histopathological findings

Group I

H&E staining showed typical myocardial architecture with normal arrangement of the muscle fibers with central nuclei and eosinophilic cytoplasm separated by fine delicate fiber strands of normal myocardium ([Figure 6]a-I).
Figure 6 A photomicrograph of cardiac muscle in all studied groups (A) H&E stain and (B) Masson’s trichrome stain showing in group I: typical myocardial architecture with normal arrangement of the muscle fibers with central nuclei and eosinophilic cytoplasm separated by fine delicate fiber strands of normal myocardium (A-I&B-I), in group II: diffuse disruption of the overall tissue architecture with marked fibrosis everywhere replacing the extensive myocardial loss (A-II&B-II), in group III: mild disruption of overall myocardial architecture with delicate strands of fibrous tissue resemble normal myocardium with minimal interstitial and perivascular inflammatory cellular infiltrates (A-III&B-III), in group IV: nearly normal myocardial architecture with scanty interstitial and perivascular inflammatory cellular infiltrates and delicate strands of fibrous tissue (A-IV&B-IV), in group V: fibrous band wider than that of group IV with more apparent disruption of myocardial architecture and degenerative changes in myocytes (A-V&B-V).

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Masson’s trichrome staining showed a very scant blue color of the connective tissue in the interstitium and around the blood vessels ([Figure 6]b-I).

Groups II

H&E staining showed both focal and extensive loss of the normal architecture of cardiac muscle fibers and myocyte degeneration with deeply stained peripheral nuclei ([Figure 6]a-II).

Masson’s trichrome staining showed marked collagen fibers with moderate interstitial edema and extensive perivascular fibrosis ([Figure 6]b-II).

In group III

H&E staining showed an overall improvement of myocardial architecture with nearly normal appearance of most of the cardiac muscle fibers with centrally located vesicular nuclei. Inflammatory cellular infiltrates were minimal ([Figure 6]a-III).

Masson’s trichrome staining showed scanty amount of interstitial fibrous materials in between the regenerated cardiac muscle fibers and in the perivascular spaces ([Figure 6]b-III).

In group IV

H&E staining showed moderate disruption of the normal architecture of the cardiac muscle fibers with degeneration of the nuclei and mild cellular inflammatory infiltrate between cardiac muscle fibers ([Figure 6]a-IV).

Masson’s trichrome stain showed focal necrosis of muscle fiber which was replaced by collagen fibers ([Figure 6]b-IV).

In group V

H&E staining showed moderate disruption of the normal architecture of the cardiac muscle fibers with degeneration of the nuclei, cellular hypertrophy, inflammatory cellular infiltrate, and moderate intercellular edema ([Figure 6]a-V).

Masson’s trichrome stain showed focal necrosis of muscle fiber with more collagen fiber deposition in the degenerated myocardium and around the blood vessels ([Figure 6]b-V).

Effect of human umbilical cord blood stem cells on the percentage of fibrosis in the myocardial tissue

Mean±SD of the percentage of fibrosis (%) in each group was 0±0, 28.8±3.6, 1.6±0.5, 5.2±1.7, and 11±2.8% in groups I, II, III, IV, and V, respectively. There was a significant decrease in the percentage of fibrosis when all HUCBSCs treated groups were compared with the MI group (P<0.001). There was a significant increase in the percentage of fibrosis when both HUCBSCs posttreated groups were compared with HUCBSCs pretreated group (P<0.001) and a significant increase when HUCBSCs posttreated within 1-week group was compared with HUCBSCs posttreated within the 24 h group (P<0.001) ([Figure 7]).
Figure 7 Comparison of the percentage of fibrosis in all studied groups. n=10 in each group. Data are represented as mean±SD. Significance (P<0.05). *Significant when compared with the control group; #significant when compared with group II; $significant when compared with group III; @significant when compared with group IV.

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Effect of human umbilical cord blood stem cells on cardiac function

There was a significant increase in LVEDd in MI (P<0.001) and HUCBSCs posttreated within 1-week (P<0.05) groups when compared with the control group, while there was a significant decrease in all HUCBSCs treated groups when compared with the MI group (P<0.05) ([Table 1]).
Table 1 Comparison of left ventricle dimensions and cardiac function in all studied groups

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There was a significant increase in LVESd in MI (P<0.001) and all HUCBSCs treated (P<0.05) groups when compared with the control group while there was a significant decrease in all HUCBSCs treated groups when compared with the MI group (P<0.001).

There was a significant decrease in LVFS and LVEF in all groups when compared with the control group (P<0.001). Moreover, there was a significant increase in LVFS and LVEF in all HUCBSCs treated groups when compared with the MI group (P<0.001) with a significant decrease in both HUCBSCs posttreated groups when compared with HUCBSCs pretreated group (P<0.001) and when HUCBSCs posttreated within 1-week group was compared with HUCBSCs posttreated within the 24 h group (P<0.05).

There was a significant decrease in MABP when all groups except HUCBSCs pretreated group was compared with the control group (P<0.001), while there was a significant increase in MABP when all HUCBSCs treated groups were compared with the MI group (P<0.001). Moreover, there was a significant decrease in MABP when both HUCBSCs posttreated groups were compared with the HUCBSCs pretreated group (P<0.05).


  Discussion Top


In the present study, MI was induced by injection of adrenaline 2 mg/kg on 2 consecutive days 24 h apart, that got aligned with other researchers who induced acute MI by the same technique [10] or who used isoproterenol as an alternative drug to induce acute MI [23]. On the contrary, another technique to induce MI by left anterior descending coronary artery ligation was used [24]. MI was confirmed by measuring troponin I and CK-MB cardiac enzymes within 24 h after MI. It was stated that troponin I and CK-MB are the most sensitive and specific enzymes used for the detection of MI. Moreover, troponin I is released within hours and remain elevated for 36 h and CK-MB reaches its peak at 14 h that fosters their use as a confirmation method [25].

Homing of HUCBSCs into the injured rat myocardium was confirmed by detecting the expression of the human β actin gene and the current study showed that its expression was higher in all HUCBSCs treated groups compared with normal and MI groups.

That agrees with Leibacher and Henschler [26] who stated that the recruitment of MSCs to ischemic heart is due to the action of the chemokine receptor signals including very late antigen-4, vascular cell adhesion protein 1, and the chemokine (C-C motif) ligand 2.

UCBSCs, in particular, are characterized by the cell surface profile of adhesion molecules correlating with a faster lung clearance and homing into damaged tissues than other types of MSCs [27] and HUCBSCs showed significant enrichment in functional gene classes involved in the liver and cardiovascular system development and function compared with MSCs derived from adipose tissue, bone marrow, and the skin [28].

On the other side, other studies have failed to detect any homed MSCs in the injured cardiac tissue over the long term [29]. Jasmin et al. [30] injected MSCs intravenously in a model of heart inflammation caused by the Trypanosoma cruzi parasite in a mouse model for Chagas disease and they observed that a few number of MSCs homed to the diseased heart while most cells migrated to the lungs, liver, and the spleen. Furthermore, it was stated that the main problem facing MSC usage for diseased tissue regeneration is the low level of recruitment and retention of cells in affected tissues; about 1% or less of systemically injected MSCs reach their target [31].

The current study showed that there was a marked reduction in cardiomyocyte apoptosis evidenced by less expression of the rat caspase-3 gene in all HUCBSCs treated groups compared with the MI group. In addition, histopathological assessment showed greater improvement with little inflammatory infiltration and fibrosis in all HUCBSCs injected groups compared with the MI one.

These results were supported by the findings of other researchers as they stated that CD105+CD34− cells MSCs secrete various paracrine factors: cytokines and growth factors that inhibit apoptosis, fibrosis, activity of immune cells, and induce angiogenesis after MI [32].

In addition, Gaebel et al. [33] compared the therapeutic potential of human MSC derived from different sources (umbilical cord blood, adipose tissue, and bone marrow). All isolated human MSC populations showed to a certain extent a therapeutic potential. Nevertheless, CD105+ showed overall a better myocardial performance. The unique immune-privileged nature of MSCs may prevent rapid rejection and preserve their ability to promote the repair of injured tissues [34].

Other studies have shown that MSC transplantation stimulates proliferation and differentiation of endogenous cardiac stem cells. This discovery can explain the replacement of scarred tissue with new contractile myocardium [35],[36].

The present study has shown that intravenous injection of HUCBSCs improved cardiac function dimensions and attenuated left ventricular remodeling, being obviously clarified by a marked improvement in ejection fraction and fractional shortening accompanied by improved MABP in all HUCBSCs treated groups compared with the MI one.These results agree with other studies that stated that MSC transplantation was beneficial for the recovery of cardiac function in experimental rats [37]. Moreover, it was stated that MSC transplants have therapeutic properties as they inhibit the inflammatory response, reduce fibrosis and infarct size, increase vascularization in postinfarction heart, and increase LVEF [32].

Regarding MABP De Morais et al. [38] reported that MSCs improved the baroreflex sensitivity, autonomic modulation, extent of MI, and collagen density in the heart, demonstrating the beneficial effects of MSC therapy on heart failure.

On the contrary, Janssens et al. [39] stated that intracoronary transfer of bone marrow stem cells within 24 h of optimum reperfusion therapy does not foster recovery of LV function after MI.

Moreover, recent meta-analysis of MSC therapy in MI clinical trials showed no difference between MSCs-treated and control groups when the LV parameters were assessed [6],[40].

The present study found that echocardiography results, expression of caspase-3 gene, and histopathological assessment showed greater improvement in HUCBSCs posttreated within the 24 h group compared with the HUCBSCs posttreated within 1-week group and the most improvement was reported in the HUCBSCs pretreated group compared with all others.

This agrees with Zhao et al. [41] who reported that HUCBSCs have a protective effect on acute MI by reducing apoptosis and promoting angiogenesis. Moreover, it was found that intravenous infusion MSCs at 24 h after acute MI reduced the infarct size and improved cardiac function after 30 days of cell transplantation [11].

It was reported that administering anti-inflammatory and antiapoptotic agents from 30 min to 24 h after myocardial ischemia/reperfusion can limit the infarct size, which promotes the role of UC-MSCs as an effective therapy within the 24 h post-MI [42].

However, it may disagree with Jiang et al. [37] whose finding showed that the most improvement was in MSC transplantation within 1-week post-MI compared with that within 1 h or that within 2 weeks post-MI and this could be because after 1 h post-MI, massive myocardial necrosis, inflammatory cells rapidly infiltrate into the ischemic myocardium, which may do harm for the survival of the implanted cells. Moreover, the Huang et al. [43] results revealed that cell therapy using intracoronary MSCs transplantation in acute MI patients that was given within 24 h is similar to 3–7 days after the primary percutaneous coronary intervention.


  Conclusion Top


HUCBSCs have high homing capability in the injured myocardium and they could be used as a preventive therapy in the case of ischemia to protect the heart from implications of MI. Moreover, it could be an effective therapy especially if administered within 24 h after MI. Further studies are recommended to highlight the preventive role of HUCBSCs and its clinical application especially in cases of unstable angina.

Acknowledgements

The authors acknowledge the staff of the Gynecology and Obstetrics Department, Clinical Pathology Department, and Stem Cell Unit, Faculty of Medicine, Zagazig University, Egypt. The histopathological assessment was done by Prof. Dr Hayam Elsaid Rashed, Assistant Professor of Pathology Department, Faculty of Medicine, Zagazig University.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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